SURFACE DISPLAY OF PROTEINS ON RECOMBINANT BACTERIA AND USES THEREOF

Abstract

Recombinant microorganisms, pharmaceutical compositions thereof, and methods of protein display on the cell surface of the microorganisms are disclosed.

Description

RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63/030,157, filed on May 26, 2020, the entire contents of which are expressly incorporated by reference herein in their entirety.

SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on May 24, 2021, is named 126046_05802_SL.txt and is 245,493 bytes in size.

BACKGROUND

[0003] Viral, bacterial, and fungal infections cause disease such as pneumonia, diarrhea, tuberculosis, and hepatitis among others. Several diseases caused by infections and cancers do not have available treatment and/or prevention therapies, or the available therapies are insufficient. Accordingly, there is a need to provide vaccines to prevent and/or treat infections, e.g., viral, bacterial, and fungal infections, and cancers.

SUMMARY

[0004] The present disclosure provides compositions, methods, and uses of microorganisms that can prevent and/or treat infections, e.g., bacterial, viral, or fungal infections. In certain aspects, the present disclosure provides recombinant microorganisms that are engineered to express one or more proteins, e.g., antigens, on their surface using, for example, a display protein. In one embodiment, the display protein is a fusion protein comprising, e.g., an anchor domain, a linker, and a displayed protein. In some embodiments, the displayed protein is viral, bacterial, or fungal, or a cancer or tumor protein. In certain aspects, the recombinant microorganism is a bacteria, e.g., Salmonella typhimurium, Escherichia coli Nissle, Clostridium novyi NT, and Clostridium butyricum miyairi, as well as other exemplary bacterial strains provided herein. Thus, in certain embodiments, the recombinant microorganisms are administered, e.g., via oral administration, intravenous injection, subcutaneous injection, intranasal delivery, or other means, and are able to generate an immune response in a host, e.g., a human, against the displayed protein of the display protein.

[0005] In one aspect, disclosed here is a recombinant microorganism capable of displaying a protein, i.e., a displayed protein. In one aspect, the displaying protein comprises an anchor domain, e.g., intimin, peptidoglycan-associated lipoprotein (PAL), PelB-PAL, YiaT, LppOmpA, BAN, OmsY, Invasin, IgA, PgsA, ice nucleation protein (INP), and NGIgAsig-NGIgAb, a linker, and the displayed protein.

[0006] In some embodiments, the nucleotide sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1489.

[0007] In some embodiments, the nucleotide sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1490.

[0008] In some embodiments, the nucleotide sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1491.

[0009] In some embodiments, the nucleotide sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1449.

[0010] In some embodiments, the nucleotide sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1492.

[0011] In some embodiments, the nucleotide sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1492.

[0012] In some embodiments, the nucleotide sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1493.

[0013] In some embodiments, the nucleotide sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1450.

[0014] In some embodiments, the nucleotide sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1494.

[0015] In some embodiments, the amino acid sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1497.

[0016] In some embodiments, the amino acid sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1498.

[0017] In some embodiments, the amino acid sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1499.

[0018] In some embodiments, the amino acid sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1464.

[0019] In some embodiments, the amino acid sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1469.

[0020] In some embodiments, the amino acid sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1500.

[0021] In some embodiments, the amino acid sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 990.

[0022] In some embodiments, the amino acid sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1465.

[0023] In some embodiments, the amino acid sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1501.

[0024] In some embodiments, the amino acid sequence of the anchor domain has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1508.

[0025] In some embodiments, the nucleotide sequence of the displayed protein has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1495. In some embodiments, the nucleotide sequence of the displayed protein has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1496. In some embodiments, the amino acid sequence of the displayed protein has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1502. In some embodiments, the amino acid sequence of the displayed protein has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1503. In some embodiments, the amino acid sequence of the displayed protein has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1505. In some embodiments, the amino acid sequence of the displayed protein has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1509. In some embodiments, the amino acid sequence of the displayed protein has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1510. In some embodiments, the amino acid sequence of the displayed protein has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1511. In some embodiments, the amino acid sequence of the displayed protein has at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity to, comprises, or consists of SEQ ID NO: 1504.

[0026] In one aspect, disclosed herein is a recombinant microorganism capable of expressing at least one displayed protein. In one aspect, disclosed herein is a recombinant microorganism capable of producing at least one immune modulator. In one aspect, disclosed herein is a recombinant microorganism capable of expressing at least one displayed protein and at least one immune modulator.

[0027] In another aspect, disclosed herein is a composition comprising a viral protein, e.g., a viral spike protein from a coronavirus, e.g., a viral spike protein receptor binding domain (RBD) from severe acute respiratory syndrome coronavirus 2 (SARS-CoV2).

[0028] In another aspect, disclosed herein is a composition comprising an immune modulator. In some embodiments, the immune modulator comprises an immune initiator, e.g., a cytokine, chemokine, single chain antibody, ligand, metabolic converter, T cell co-stimulatory receptor, T cell co-stimulatory receptor ligand, or lytic peptide. In some embodiments, the immune modulator comprises an immune modulator, e.g., a chemokine, a cytokine, a single chain antibody, a ligand, a metabolic converter, a T cell co-stimulatory receptor, or a T cell co-stimulatory receptor ligand.

[0029] In another aspect, disclosed herein is a composition comprising a first recombinant microorganism capable of expressing at least one display protein and at least a second recombinant microorganism capable of producing at least one immune modulator.

[0030] In one embodiment, the immune initiator is capable of enhancing oncolysis, activating antigen presenting cells (APCs), and/or priming and activating T cells. In another embodiment, the immune initiator is capable of enhancing oncolysis. In another embodiment, the immune initiator is capable of activating APCs. In yet another embodiment, the immune initiator is capable of priming and activating T cells.

[0031] In one embodiment, the microorganism induces a CTL response to a virus. In one embodiment, the microorganism produces a CTL response against epitopes in the viral nucleocapsid (N) and/or M protein. Such proteins and epitopes are well known in the art and described at least in Liu et al., Antiviral Research 137 (2017), 82-92; Huang et al., Vaccine 25 (2007):6981-6991; Ahmed et al., Viruses (2020) 12:254; Grifoni et al., Cell Host & Microbiome (2020) 27:1-10; and Chen et al., J. Immunol (2005) 175:591-598, the entire contents of each of which are expressly incorporated by reference herein in their entireties.

[0032] In one embodiment, the immune initiator is a therapeutic molecule encoded by at least one gene. In one embodiment, the immune initiator is a therapeutic molecule produced by an enzyme encoded by at least one gene. In one embodiment, the immune imitator is at least one enzyme of a biosynthetic pathway or a catabolic pathway encoded by at least one gene. In one embodiment, the immune imitator is at least one therapeutic molecule produced by at least one enzyme of a biosynthetic pathway or a catabolic pathway encoded by at least one gene. In one embodiment, the immune imitator is a nucleic acid molecule that mediates RNA interference, microRNA response or inhibition, TLR response, antisense gene regulation, target protein binding, or gene editing.

[0033] In one embodiment, the immune imitator is a cytokine, a chemokine, a single chain antibody, a ligand, a metabolic converter, a T cell co-stimulatory receptor, a T cell co-stimulatory receptor ligand, or a lytic peptide. In one embodiment, the immune initiator is a secreted peptide or a displayed peptide.

[0034] In one embodiment, the immune initiator is a STING agonist, arginine, 5-FU, TNF.alpha., IFN.gamma., IFN.beta.1, agonistic anti-CD40 antibody, CD40L, SIRP.alpha., GMCSF, agonistic anti-OX040 antibody, OXO40L, agonistic anti-4-1BB antibody, 4-1BBL, agonistic anti-GITR antibody, GITRL, anti-PD1 antibody, anti-PDL1 antibody, or azurin. In one embodiment, the immune initiator is a STING agonist. In one embodiment, the immune initiator is at least one enzyme of an arginine biosynthetic pathway. In one embodiment, the immune initiator is arginine. In one embodiment, the immune initiator is 5-FU. In one embodiment, the immune initiator is TNF.alpha.. In one embodiment, the immune initiator is IFN.gamma.. In one embodiment, the immune initiator is IFN.beta.1. In one embodiment, the immune initiator is an agonistic anti-CD40 antibody. In one embodiment, the immune initiator is SIRP.alpha.. In one embodiment, the immune initiator is CD40L. In one embodiment, the immune initiator is GMCSF. In one embodiment, the immune initiator is an agonistic anti-OX040 antibody. In another embodiment, the immune initiator is OXO40L. In one embodiment, the immune initiator is an agonistic anti-4-1BB antibody. In one embodiment, the immune initiator is 4-1BBL. In one embodiment, the immune initiator is an agonistic anti-GITR antibody. In another embodiment, the immune initiator is GITRL. In one embodiment, the immune initiator is an anti-PD1 antibody. In one embodiment, the immune initiator is an anti-PDL1 antibody. In one embodiment, the immune initiator is azurin.

[0035] In one embodiment, the immune initiator is a STING agonist. In one embodiment, the STING agonist is c-diAMP. In one embodiment, the STING agonist is c-GAMP. In one embodiment, the STING agonist is c-diGMP.

[0036] In one embodiment, the recombinant microorganism comprises at least one gene sequence encoding an enzyme which produces the immune initiator. In one embodiment, the at least one gene sequence encoding the immune initiator is a dacA gene sequence. In one embodiment, the at least one gene sequence encoding the immune initiator is a cGAS gene sequence. In one embodiment, the cGAS gene sequence is a human cGAS gene sequence. In one embodiment, the cGAS gene sequence is selected from a human cGAS gene sequence a Verminephrobacter eiseniae cGAS gene sequence, Kingella denitrificans cGAS gene sequence, and a Neisseria bacilliformis cGAS gene sequence.

[0037] In one embodiment, the at least one gene sequence encoding the immune initiator is integrated into a chromosome of the recombinant microorganism. In one embodiment, the at least one gene sequence encoding the immune initiator is present on a plasmid. In one embodiment, the at least one gene sequence encoding the immune initiator is operably linked to an inducible promoter. In one embodiment, the inducible promoter is induced by low oxygen, anaerobic, or hypoxic conditions.

[0038] In one embodiment, the immune initiator is arginine. In another embodiment, the immune initiator is at least one enzyme of an arginine biosynthetic pathway.

[0039] In one embodiment, the microorganism comprises at least one gene sequence encoding the at least one enzyme of the arginine biosynthetic pathway. In one embodiment, the at least one gene sequence encoding the at least one enzyme of the arginine biosynthetic pathway comprises feedback resistant argA. In one embodiment, the at least one gene sequence encoding the at least one enzyme of the arginine biosynthetic pathway is selected from the group consisting of: argA, argB, argC, argD, argE, argF, argG, argH, argI, argJ, carA, and carB. In one embodiment, the microorganism further comprises a deletion or a mutation in an arginine repressor gene (argR). In one embodiment, the at least one gene sequence for the production of arginine is integrated into a chromosome of the recombinant microorganism. In one embodiment, the at least one gene sequence for the production of arginine is present on a plasmid. In one embodiment, the at least one gene sequence for the production of arginine is operably linked to an inducible promoter. In one embodiment, the inducible promoter is induced by low oxygen, anaerobic, or hypoxic conditions.

[0040] In one embodiment, the immune initiator is 5-FU.

[0041] In one embodiment, the microorganism comprises at least one gene sequence encoding an enzyme capable of converting 5-FC to 5-FU. In one embodiment, the at least one gene sequence is codA. In one embodiment, the at least one gene sequence is integrated into a chromosome of the recombinant microorganism. In another embodiment, the at least one gene sequence is present on a plasmid. In one embodiment, the at least one gene sequence encoding the immune initiator is operably linked to an inducible promoter. In one embodiment, the inducible promoter is an FNR promoter.

[0042] In one embodiment, the immune sustainer is capable of enhancing trafficking and infiltration of T cells, enhancing recognition of target cells by T cells, enhancing effector T cell response, and/or overcoming immune suppression. In one embodiment, the immune sustainer is capable of enhancing trafficking and infiltration of T cells. In one embodiment, the immune sustainer is capable of enhancing recognition of target cells by T cells. In one embodiment, the immune sustainer is capable of enhancing effector T cell response. In one embodiment, the immune sustainer is capable of overcoming immune suppression.

[0043] In one embodiment, the immune sustainer is a therapeutic molecule encoded by at least one gene. In one embodiment, the immune sustainer is a therapeutic molecule produced by an enzyme encoded by at least one gene. In one embodiment, the immune sustainer is at least one enzyme of a biosynthetic or catabolic pathway encoded by at least one gene. In one embodiment, the immune sustainer is at least one therapeutic molecule produced by at least one enzyme of a biosynthetic or catabolic pathway encoded by at least one gene. In one embodiment, the immune sustainer is a nucleic acid molecule that mediates RNA interference, microRNA response or inhibition, TLR response, antisense gene regulation, target protein binding, or gene editing.

[0044] In one embodiment, the immune sustainer is a cytokine, a chemokine, a single chain antibody, a ligand, a metabolic converter, a T cell co-stimulatory receptor, a T cell co-stimulatory receptor ligand, or a secreted or displayed peptide.

[0045] In one embodiment, the immune sustainer is a metabolic converter, arginine, a STING agonist, CXCL9, CXCL10, anti-PD1 antibody, anti-PDL1 antibody, anti-CTLA4 antibody, agonistic anti-GITR antibody or GITRL, agonistic anti-OX40 antibody or OX40L, agonistic anti-4-1BB antibody or 4-1BBL, IL-15, IL-15 sushi, IFN.gamma., or IL-12. In one embodiment, the immune sustainer is a secreted peptide or a displayed peptide.

[0046] In one embodiment, the immune sustainer is a metabolic converter. In one embodiment, the metabolic converter is at least one enzyme of a kynurenine consumption pathway. In another embodiment, the metabolic converter is at least one enzyme of an adenosine consumption pathway. In another embodiment, the metabolic converter is at least one enzyme of an arginine biosynthetic pathway.

[0047] In one embodiment, the microorganism comprises at least one gene sequence encoding the at least one enzyme of the kynurenine consumption pathway. In one embodiment, the at least one gene sequence encoding the at least one enzyme of the kynurenine consumption pathway is a kynureninase gene sequence. In one embodiment, he at least one gene sequence is kynU. In one embodiment, the at least one gene sequence is operably linked to a constitutive promoter. In one embodiment, the at least one gene sequence encoding the at least one enzyme of the kynurenine consumption pathway is integrated into a chromosome of the microorganism. In another embodiment, the at least one gene sequence encoding the at least one enzyme of the kynurenine consumption pathway is present on a plasmid. In one embodiment, the microorganism comprises a deletion or a mutation in trpE.

[0048] In one embodiment, the microorganism comprises at least one gene sequence encoding at least one enzyme of an adenosine consumption pathway. In one embodiment, the at least one gene sequence encoding the at least one enzyme of the adenosine consumption pathway is selected from add, xapA, deoD, xdhA, xdhB, and xdhC. In one embodiment, the at least one gene sequence encoding the at least one enzyme of the adenosine consumption pathway is operably linked to a promoter induced by low oxygen, anaerobic, or hypoxic conditions. In one embodiment, the at least one gene sequence encoding the at least one enzyme of the adenosine consumption pathway is integrated into a chromosome of the microorganism. In another embodiment, the at least one gene sequence is present on a plasmid. In one embodiment, the recombinant microorganism comprises at least one gene sequence encoding an enzyme for importing adenosine into the microorganism. In one embodiment, the at least one gene sequence encoding the enzyme for importing adenosine into the microorganism is nupC or nupG.

[0049] In one embodiment, the immune sustainer is arginine. In one embodiment, the microorganism comprises at least one gene sequence encoding at least one enzyme of the arginine biosynthetic pathway. In one embodiment, the at least one gene sequence encoding at least one enzyme of the arginine biosynthetic pathway comprises feedback resistant argA. In one embodiment, the at least one gene sequence encoding the at least one enzyme of the arginine biosynthetic pathway is selected from the group consisting of: argA, argB, argC, argD, argE, argF, argG, argH, argI, argJ, carA, and carB. In one embodiment, the at least one gene sequence encoding the at least one enzyme of the arginine biosynthetic pathway is operably linked to a promoter induced by low oxygen, anaerobic, or hypoxic conditions. In one embodiment, the at least one gene sequence encoding the at least one enzyme of the arginine biosynthetic pathway is integrated into a chromosome of the recombinant microorganism or is present on a plasmid. In one embodiment, the microorganism further comprises a deletion or a mutation in an arginine repressor gene (argR).

[0050] In one embodiment, the immune sustainer is a STING agonist. In one embodiment, the STING agonist is c-diAMP, c-GAMP, or c-diGMP. In another embodiment, the recombinant microorganism comprises at least one gene sequence encoding an enzyme which produces the STING agonist. In one embodiment, the at least one gene sequence encoding the immune sustainer is a dacA gene sequence. In one embodiment, the at least one gene sequence encoding the immune sustainer is a cGAS gene sequence. In one embodiment, the cGAS gene sequence is selected from a human cGAS gene sequence, a Verminephrobacter eiseniae cGAS gene sequence, Kingella denitrificans cGAS gene sequence, and a Neisseria bacilliformis cGAS gene sequence.

[0051] In one embodiment, the immune initiator is not the same as the immune sustainer. In one embodiment, the immune initiator is different than the immune sustainer.

[0052] In one embodiment, the recombinant microorganism comprises at least one gene sequence encoding an enzyme capable of producing the STING agonist. In one embodiment, the at least one gene sequence encoding the STING agonist is a dacA gene. In one embodiment, the at least one gene sequence encoding the STING agonist is a cGAS gene. In one embodiment, the STING agonist is c-diAMP. In one embodiment, the STING agonist is c-GAMP. In one embodiment, the STING agonist is c-diGMP.

[0053] In one embodiment, the bacterium is an auxotroph in a gene that is not complemented when the bacterium is present in a host. In one embodiment, the gene that is not complemented when the bacterium is present in a host is a dapA gene. In one embodiment, expression of the dapA gene fine-tunes the expression of the one or more immune initiators. In one embodiment, the bacterium is an auxotroph in a gene that is complemented when the bacterium is present in a host. In one embodiment, the gene that is complemented when the bacterium is present in a host is a thyA gene.

[0054] In one embodiment, the bacterium further comprises a mutation or deletion in an endogenous prophage.

[0055] In one embodiment, the at least one gene sequence is operably linked to an inducible promoter. In one embodiment, the inducible promoter is induced by low-oxygen or anaerobic conditions. In one embodiment, the inducible promoter is induced by a hypoxic environment. In one embodiment, the promoter is an FNR promoter.

[0056] In one embodiment, the at least one gene sequence is integrated into a chromosome in the bacterium. In one embodiment, the at least one gene sequence is located on a plasmid in the bacterium.

[0057] In one embodiment, the bacterium is non-pathogenic. In one embodiment, he bacterium is Escherichia coli Nissle.

[0058] In one aspect, disclosed herein is a recombinant microorganism capable of producing an effector molecule, wherein the effector molecule is selected from the group consisting of CXCL9, CXCL10, hyaluronidase, and SIRP.alpha..

[0059] In one embodiment, the recombinant microorganism comprises at least one gene sequence encoding CXCL9. In one embodiment, the at least one gene sequence encoding CXCL9 is linked to an inducible promoter.

[0060] In one embodiment, the recombinant microorganism comprises at least one gene sequence encoding CXCL10. In one embodiment, the at least one gene sequence encoding CXCL10 is linked to an inducible promoter.

[0061] In one embodiment, the recombinant microorganism comprises at least one gene sequence encoding hyaluronidase. In one embodiment, the at least one gene sequence encoding hyaluronidase is linked to an inducible promoter.

[0062] In one embodiment, the recombinant microorganism comprises at least one gene sequence encoding the SIRP.alpha.. In one embodiment, the at least one gene sequence encoding the SIRP.alpha. is linked to an inducible promoter.

[0063] In one embodiment, the effector molecule is secreted. In another embodiment, the effector molecule is displayed on the cell surface.

[0064] In one aspect, disclosed herein is a recombinant microorganism capable of converting 5-FC to 5-FU. In another aspect, disclosed herein is a recombinant microorganism capable of converting 5-FC to 5-FU, wherein the recombinant microorganism is further capable of producing a STING agonist.

[0065] In one embodiment, the microorganism comprises at least one gene sequence encoding an enzyme capable of converting 5-FC to 5-FU. In one embodiment, the at least one gene sequence is codA. In one embodiment, the at least one gene sequence is a codA::upp fusion. In one embodiment, the at least one gene sequence is operably linked to an inducible promoter or a constitutive promoter. In one embodiment, the inducible promoter is a FNR promoter. In one embodiment, the at least one gene sequence is integrated into the chromosome of the microorganism or is present on a plasmid.

[0066] In one embodiment, the microorganism capable of converting 5-FC to 5-FU is further capable of producing a STING agonist. In one embodiment, the STING agonist is c-diAMP, c-GAMP, or c-diGMP. In one embodiment, the recombinant microorganism comprises at least one gene sequence encoding an enzyme which produces the STING agonist. In one embodiment, the at least one gene sequence encoding the enzyme which produces the STING agonist is a dacA gene sequence. In one embodiment, the at least one gene sequence encoding the enzyme which produces the STING agonist is a cGAS gene sequence. In one embodiment, the cGAS gene sequence is a human cGAS gene sequence. In one embodiment, the at least one gene sequence encoding the enzyme which produces the STING agonist is operably linked to an inducible promoter. In one embodiment, the inducible promoter is an FNR promoter. In one embodiment, the at least one gene sequence encoding the enzyme which produces the STING agonist is integrated into a chromosome of the microorganism or is present on a plasmid.

[0067] In one embodiment, the recombinant microorganism disclosed herein is a bacterium. In one embodiment, the recombinant microorganism disclosed herein is a yeast. In one embodiment, the recombinant microorganism is an E. coli bacterium. In one embodiment, the recombinant microorganism is an E. coli Nissle bacterium. In one embodiment, the recombinant microorganism is E. coli Nissle strain SYN1557 (delta PAL::CmR).

[0068] In one embodiment, the recombinant microorganism disclosed herein comprises at least one mutation or deletion in a gene which results in one or more auxotrophies. In one embodiment, the at least one deletion or mutation is in a dapA gene and/or a thyA gene.

[0069] In one embodiment, the recombinant microorganism disclosed herein comprises a phage deletion.

[0070] In one aspect, disclosed herein is a composition comprising at least a first recombinant microorganism capable of expressing at least one display protein comprising a viral antigen, and at least a second recombinant microorganism capable of producing an immune modulator.

[0071] In one aspect, disclosed herein is a composition comprising at least a first recombinant microorganism capable of expressing at least one display protein comprising a cancer antigen, and at least a second recombinant microorganism capable of producing an immune modulator.

[0072] In one aspect, disclosed herein is a composition comprising a viral protein and at least one recombinant microorganism capable of producing an immune modulator. In one embodiment, the at least one recombinant microorganism is capable of producing both the immune initiator and the immune sustainer. In another embodiment, the at least one recombinant microorganism is capable of producing the immune initiator, and at least a second recombinant microorganism is capable of producing the immune sustainer. In yet another embodiment, the immune sustainer is not produced by a recombinant microorganism in the composition. In another embodiment, the at least one recombinant microorganism is capable of producing the immune sustainer, and at least a second recombinant microorganism is capable of producing the immune initiator. In yet another embodiment, the immune initiator is not produced by a recombinant microorganism in the composition.

[0073] In one embodiment, the immune initiator is not arginine, TNF.alpha., IFN.gamma., IFN.beta.1, GMCSF, anti-CD40 antibody, CD40L, agonistic anti-OX40 antibody, OX040L, agonistic anti-41BB antibody, 41BBL, agonistic anti-GITR antibody, GITRL, anti-PD1 antibody, anti-PDL1 antibody, and/or azurin. In one embodiment, the immune initiator is not arginine. In one embodiment, the immune initiator is not TNF.alpha.. In one embodiment, the immune initiator is not IFN.gamma.. In one embodiment, the immune initiator is not IFN.beta.1. In one embodiment, the immune initiator is not an anti-CD40 antibody. In one embodiment, the immune initiator is not CD40L. In one embodiment, the immune initiator is not GMCSF. In one embodiment, the immune initiator is not an agonistic anti-OX040 antibody. In one embodiment, the immune initiator is not OX040L. In one embodiment, the immune initiator is not an agonistic anti-4-1BB antibody. In one embodiment, the immune initiator is not 4-1BBL. In one embodiment, the immune initiator is not an agonistic anti-GITR antibody. In one embodiment, the immune initiator is not GITRL. In one embodiment, the immune initiator is not an anti-PD1 antibody. In one embodiment, the immune initiator is not an anti-PDL1 antibody. In one embodiment, the immune initiator is not azurin.

[0074] In one embodiment, the immune sustainer is not at least one enzyme of a kynurenine consumption pathway, at least one enzyme of an adenosine consumption pathway, anti-PD1 antibody, anti-PDL1 antibody, anti-CTLA4 antibody, IL-15, IL-15 sushi, IFN.gamma., agonistic anti-GITR antibody, GITRL, an agonistic anti-OX40 antibody, OX40L, an agonistic anti-4-1BB antibody, 4-1BBL, or IL-12. In one embodiment, the immune sustainer is not at least one enzyme of a kynurenine consumption pathway. In one embodiment, the immune sustainer is not at least one enzyme of an adenosine consumption pathway. In one embodiment, the immune sustainer is not arginine. In one embodiment, the immune sustainer is not at least one enzyme of an arginine biosynthetic pathway. In one embodiment, the immune sustainer is not an anti-PD1 antibody. In one embodiment, the immune sustainer is not an anti-PDL1 antibody. In one embodiment, the immune sustainer is not an anti-CTLA4 antibody. In one embodiment, the immune sustainer is not an agonistic anti-GITR antibody. In one embodiment, the immune sustainer is not GITRL. In one embodiment, the immune sustainer is not IL-15. In one embodiment, the immune sustainer is not IL-15 sushi. In one embodiment, the immune sustainer is not IFN.gamma.. In one embodiment, the immune sustainer is not an agonistic anti-OX40 antibody. In one embodiment, the immune sustainer is not OX40L. In one embodiment, the immune sustainer is not an agonistic anti-4-1BB antibody. In one embodiment, the immune sustainer is not 4-1BBL. In one embodiment, the immune sustainer is not IL-12.

[0075] In one aspect, disclosed herein is a pharmaceutically acceptable composition comprising a recombinant microorganism disclosed herein, and a pharmaceutically acceptable carrier. In one aspect, disclosed herein is a pharmaceutically acceptable composition comprising a composition disclosed herein, and a pharmaceutically acceptable carrier. In one embodiment, the composition is formulated for intranasal delivery. In one embodiment, the pharmaceutically acceptable composition is for use in treating a subject having a bacterial, viral, or fungal infection. In one embodiment, the pharmaceutically acceptable composition is for preventing a bacterial, viral, or fungal infection in a subject. In another embodiment, the pharmaceutically acceptable composition is for use in treating a subject having an coronavirus infection. In another embodiment, the pharmaceutically acceptable composition is for use in treating a subject having the coronavirus disease 2019 (COVID-19). In one embodiment, the pharmaceutically acceptable composition is for treating cancer in a subject. In another embodiment, the pharmaceutically acceptable composition is for use in inducing and modulating an immune response in a subject.

[0076] In one aspect, disclosed herein is a kit comprising a pharmaceutically acceptable composition disclosed herein, and instructions for use thereof.

[0077] In one aspect, disclosed herein is a method of treating a bacterial, viral, or fungal infection in a subject, the method comprising administering to the subject a pharmaceutically acceptable composition disclosed herein, thereby treating the bacterial, viral, or fungal infection in the subject.

[0078] In one aspect, disclosed herein is a method of treating the coronavirus disease 2019 (COVID-19) in a subject, the method comprising administering to the subject a pharmaceutically acceptable composition disclosed herein, thereby treating the coronavirus disease 2019 (COVID-19) in the subject.

[0079] In one aspect, disclosed herein is a method of treating cancer in a subject, the method comprising administering to the subject a pharmaceutically acceptable composition disclosed herein, thereby treating the cancer in the subject.

[0080] In one aspect, disclosed herein is a method of inducing and sustaining an immune response in a subject, the method comprising administering to the subject a pharmaceutically acceptable composition disclosed herein, thereby inducing and sustaining the immune response in the subject.

[0081] In one aspect, disclosed herein is a method of inducing and sustaining an immune response in a subject, the method comprising administering to the subject a pharmaceutically acceptable composition described herein, thereby inducing and sustaining the immune response in the subject.

[0082] In one aspect, disclosed herein is a method of treating a microbial infection in a subject, the method comprising administering a first recombinant microorganism to the subject, wherein the first recombinant microorganism is capable of expressing a display protein; and administering a second recombinant microorganism to the subject, wherein the second recombinant microorganism is capable of producing an immune modulator, thereby treating the microbial infection in the subject.

[0083] In one aspect, disclosed herein is a method of treating cancer in a subject, the method comprising administering a first recombinant microorganism to the subject, wherein the first recombinant microorganism is capable of expressing a cancer protein on its cell surface; and administering a second recombinant microorganism to the subject, wherein the second recombinant microorganism is capable of producing an immune modulator, thereby treating cancer in the subject.

[0084] In one aspect, disclosed herein is a method of treating the coronavirus disease 2019 (COVID-19) in a subject, the method comprising administering a first recombinant microorganism to the subject, wherein the first recombinant microorganism is capable of producing a viral protein; and administering a second recombinant microorganism to the subject, wherein the second recombinant microorganism is capable of producing an immune modulator, thereby treating the coronavirus disease 2019 (COVID-19) in the subject.

[0085] In one aspect, disclosed herein is a method of inducing and sustaining an immune response in a subject, the method comprising administering a first recombinant microorganism to the subject, wherein the first recombinant microorganism is capable of producing a viral protein; and administering a second recombinant microorganism to the subject, wherein the second recombinant microorganism is capable of producing an immune modulator, thereby inducing and sustaining the immune response in the subject.

[0086] In one embodiment, the administering steps are performed at the same time. In one embodiment, the administering of the first recombinant microorganism to the subject occurs before the administering of the second recombinant microorganism to the subject. In one embodiment, the administering of the second recombinant microorganism to the subject occurs before the administering of the first recombinant microorganism to the subject.

[0087] In one aspect, disclosed herein is a method of treating a microbial infection in a subject, the method comprising administering a first recombinant microorganism to the subject, wherein the first recombinant microorganism is capable of displaying a display protein on its surface; and administering an immune modulator to the subject, thereby treating the microbial infection in the subject.

[0088] In one aspect, disclosed herein is a method of treating cancer in a subject, the method comprising administering a first recombinant microorganism to the subject, wherein the first recombinant microorganism is capable of expressing a protein on its surface via a display protein; and administering an immune modulator to the subject, thereby treating cancer in the subject.

[0089] In one aspect, disclosed herein is a method of treating the coronavirus disease 2019 (COVID-19) in a subject, the method comprising administering a first recombinant microorganism to the subject, wherein the first recombinant microorganism is capable of displaying a viral protein; and administering an immune modulator to the subject, thereby treating the coronavirus disease 2019 (COVID-19) in the subject.

[0090] In one aspect, disclosed herein is a method of inducing and sustaining an immune response in a subject, the method comprising administering a first recombinant microorganism to the subject, wherein the first recombinant microorganism is capable of displaying a viral protein; and administering an immune modulator to the subject, thereby inducing and sustaining the immune response in the subject.

[0091] In one embodiment, the administering steps are performed at the same time. In one embodiment, the administering of the first recombinant microorganism to the subject occurs before the administering of the immune sustainer to the subject. In another embodiment, the administering of the immune sustainer to the subject occurs before the administering of the first recombinant microorganism to the subject.

[0092] In one aspect, disclosed herein is a method of treating a microbial infection in a subject, the method comprising administering a protein to the subject; and administering a first recombinant microorganism to the subject, wherein the first recombinant microorganism is capable of producing an immune modulator, thereby treating the microbial infection in the subject.

[0093] In one aspect, disclosed herein is a method of treating the coronavirus disease 2019 (COVID-19) in a subject, the method comprising administering a viral protein to the subject; and administering a first recombinant microorganism to the subject, wherein the first recombinant microorganism is capable of producing an immune modulator, thereby treating the coronavirus disease 2019 (COVID-19) in the subject.

[0094] In one aspect, disclosed herein is a method of inducing and sustaining an immune response in a subject, the method comprising administering a viral protein to the subject; and administering a first recombinant microorganism to the subject, wherein the first recombinant microorganism is capable of producing an immune modulator, thereby inducing and sustaining the immune response in the subject.

[0095] In one embodiment, the administering steps are performed at the same time. In one embodiment, the administering of the first recombinant microorganism to the subject occurs before the administering of the immune initiator to the subject. In one embodiment, the administering of the immune initiator to the subject occurs before the administering of the first recombinant microorganism to the subject.

[0096] In one embodiment, the administering is intranasal injection.

[0097] Accordingly, the disclosure provides compositions comprising one or more modified bacteria comprising gene sequence(s) encoding one or more immune modulators. In some embodiments, the immune modulator is an immune initiator, which may for example modulate, e.g., promote cell lysis, antigen presentation by dendritic cells or macrophages, or T cell activation or priming. Examples of such immune initiators include cytokines or chemokines, such as TNF.alpha., IFN-gamma and IFN-beta1, a single chain antibodies, such as anti-CD40 antibodies, or (3) ligands such as SIRP.alpha. or CD40L, a metabolic enzymes (biosynthetic or catabolic), such as a STING agonist producing enzyme, or (5) cytotoxic chemotherapies. The immune modulators, e.g., immune initiators, may be operably linked to a promoter not associated with the gene sequence(s) in nature.

[0098] In some embodiments, the genetically engineered bacteria are capable of producing one or more STING agonist(s), such as c-di-AMP, 3'3'-cGAMP and/or c-2'3'-cGAMP. In some embodiments, the genetically engineered bacteria comprise gene sequences encoding a diadenylate cyclase, such as DacA, e.g., from Listeria monocytogenes. In some embodiments, the genetically engineered bacteria comprise gene sequences encoding a 3'3'-cGAMP synthase. Non-limiting examples of 3'3'-cGAMP synthases described in the instant disclosure include 3'3'-cGAMP synthase Verminephrobacter eiseniae (EF01-2 Earthworm symbiont), 3'3'-cGAMP synthase from Kingella denitrificans (ATCC 33394), and 3'3'-cGAMP synthase from Neisseria bacilliformis (ATCC BAA-1200). In some embodiments, the genetically engineered bacteria comprise gene sequences encoding a 2'3'-cGAMP synthase, such as human cGAS.

[0099] In some embodiments, the genetically engineered bacteria comprise gene sequences encoding agonists of co-stimulatory receptors, including but not limited to OX40, GITR, 41BB.

[0100] In some embodiments, the composition further comprises one or more genetically engineered microorganism(s) comprising gene sequence(s) for producing an immune sustainer. Such a sustainer may be selected from a cytokine or chemokine, a single chain antibody antagonistic peptide or ligand, and a metabolic enzyme pathways.

[0101] Examples of immune sustaining cytokines which may be produced by the genetically engineered bacteria include IL-15 and CXCL10, which may be secreted into the microenvironment. Non-limiting examples of single chain antibodies include anti-PD-1, anti-PD-L1, or anti-CTLA-4, which may be secreted into the microenvironment or displayed on the microorganism cell surface.

[0102] In some embodiments, the genetically engineered bacteria comprise gene sequences encoding circuitry for one or more metabolic conversions, i.e., the bacteria are capable performing one or more enzyme-catalyzed reactions, which can be either biosynthetic or catabolic in nature. Accordingly, in some embodiments, the genetically engineered bacteria are capable of producing metabolites which modulate, e.g., promote or contribute to immune initiation and/or immune sustenance or are capable of consuming metabolites which modulate, e.g., inhibit viral infection.

[0103] In any of these compositions, the promoter operably linked to the gene sequences(s) for producing the immune modulator, e.g., the immune initiator and/or immune sustainer may an inducible promoter. In some embodiments, the promoter is induced by low-oxygen or anaerobic conditions, such as by a hypoxic environment. Non-limiting examples of such low oxygen inducible promoters of the disclosure include FNR-inducible promoters, ANR-inducible promoters, and DNR-inducible promoters. In some embodiments, the promoter operably linked to the gene sequence(s) for producing the immune modulator, e.g., the immune initiator or immune sustainer, is directly or indirectly induced by a chemical inducer that is not normally present. In some embodiments, the promoter is induced in vitro during fermentation in a suitable growth vessel. In some embodiments, the chemical inducer is selected from tetracycline, IPTG, arabinose, cumate, and salicylate.

[0104] In some embodiments, the composition comprises bacteria that are auxotrophs for a particular metabolite, e.g., the bacterium is an auxotroph in a gene that is not complemented when the microorganism(s) is present in the host. In some embodiments, the bacterium is an auxotroph in the DapA gene. In some embodiments, the composition comprises bacteria that are auxotrophs for a particular metabolite, e.g., the bacterium is an auxotroph in a gene that is complemented when the microorganism(s) is present in the host. In some embodiments, the bacterium is an auxotroph in the ThyA gene. In some embodiments, the bacterium is an auxotroph in the TrpE gene.

[0105] In some embodiments, the bacterium is a Gram-positive bacterium. In some embodiments, the bacterium is a Gram-negative bacterium. In some embodiments, the bacterium is an obligate anaerobic bacterium. In some embodiments, the bacterium is a facultative anaerobic bacterium. Non-limiting examples of bacteria contemplated in the disclosure include Clostridium novyi NT, and Clostridium butyricum, and Bifidobacterium longum. In some embodiments, the bacterium is selected from E. coli Nissle, and E. coli K-12.

[0106] In some embodiments, the bacterium comprises an antibiotic resistance gene sequence. In some embodiments, the one or more of the gene sequence(s) encoding the immune modulator(s) are present on a chromosome. In some embodiments, the one or more of the gene sequence(s) encoding the immune modulator(s) are present on a plasmid.

[0107] Additionally, pharmaceutical compositions are provided, further comprising one or more immune checkpoint inhibitors, such as CTLA-4 inhibitor, a PD-1 inhibitor, and a PD-L1 inhibitor. Such checkpoint inhibitors may be administered in combination, sequentially or concurrently with the genetically engineered bacteria.

[0108] Additionally, pharmaceutical compositions are provided, further comprising one or more agonists of co-stimulatory receptors, such as OX40, GITR, and/or 41BB, including but not limited to agonistic molecules, such as ligands or agonistic antibodies which are capable of binding to co-stimulatory receptors, such as OX40, GITR, and/or 41BB. Such agonistic molecules may be administered in combination, sequentially or concurrently with the genetically engineered bacteria.

[0109] In any of these embodiments, a combination of engineered bacteria can be used in conjunction with conventional anti-viral therapies. In any of these embodiments, the engineered bacteria can produce one or more cytotoxins or lytic peptides. In any of these embodiments, the engineered bacteria can be used in conjunction with a viral vaccine.

[0110] In one embodiment, disclosed herein is a modified bacterium comprising at least one an immune initiator, wherein the immune initiator is capable of producing a stimulator of interferon gene (STING) agonist.

BRIEF DESCRIPTION OF THE FIGURES

[0111] FIG. 1 depicts a schematic showing surface display on the outer membrane including an anchor domain, a linker, and a displayed reporter.

[0112] FIG. 2 depicts surface display of GFP and FLAG tag analyzed by flow cytometry. E. coli Nissle cells containing a negative control or one of three constructs each containing a different anchor domain, and FLAG tag, and GFP were analyzed.

[0113] FIG. 3 depicts surface display of GFP and FLAG tag analyzed by flow cytometry. A negative control was compared to three constructs each containing a different anchor domain, a FLAG tag, and GFP. Invasin N, yiaT, and intimin N were compared as anchor domains.

[0114] FIGS. 4A, 4B, and 5A, 5B, and 5C depict additional flow cytometry analysis of constructs including different anchor domains, a FLAG tag, and GFP.

[0115] FIG. 6 depicts a schematic showing Nissle surface display of nanobody A4 binding to CD47. In vitro staining shows binding of A4 protein by recombinant CD47 protein using E. coli Nissle cells displaying A4 on the membrane.

[0116] FIG. 7 depicts surface display of A4 protein incubated with or without CD47 and analyzed by flow cytometry.

[0117] FIG. 8 depicts histogram plots of surface display of EGFR analyzed by flow cytometry.

[0118] FIG. 9 depicts a schematic showing the product concept for engineered E. coli Nissle vaccine design and mechanism of action.

[0119] FIG. 10 depicts a schematic showing the STING Pathway in Antigen Presenting Cells.

[0120] FIG. 11 depicts the design of S protein antigen variants for Nissle surface display.

[0121] FIGS. 12, 13, and 14 depict additional exemplary designs of S protein antigen variants for Nissle surface display.

DETAILED DESCRIPTION

[0122] The disclosure relates to recombinant microorganisms, e.g., recombinant bacteria, pharmaceutical compositions thereof, and methods of preventing or treating infections, e.g., viral, bacterial, or fungal infections. In certain aspects, the compositions and methods disclosed herein may be used to display and deliver one or more viral, bacterial, fungal, or cancer protein and/or immune modulators to a host/host cells to prevent and/or treat viral, bacterial, or fungal infections. In one embodiment, the microorganism is a vaccine.

[0123] This disclosure relates to compositions and therapeutic methods for the local and target-specific display and/or delivery of one or more viral, bacterial, fungal, or cancer protein and/or immune modulators in order to prevent and/or treat viral, bacterial, or fungal infection and/or diseases, e.g., COVID-19. In certain aspects, the disclosure relates to genetically engineered microorganisms that are capable of producing one or more effector molecules e.g., immune modulators, such as any of the effector molecules provided herein. In certain aspects, the disclosure relates to genetically engineered bacteria that are capable of producing one or more effector molecules, e.g., immune modulators(s).

[0124] Specifically, in some embodiments, the genetically engineered bacteria are capable of producing one or more viral proteins. In some embodiments the genetically engineered bacteria are capable of producing one or more immune modulators in combination with one or more viral proteins. In one embodiment, the subject to which the bacteria are delivered generate and sustain an immune response against the one or more viral proteins, thereby preventing and/or treating COVID-19 in the subject.

[0125] Specifically, in some embodiments, the genetically engineered bacteria are capable of producing one or more viral, bacterial, fungal, or cancer protein. In some embodiments the genetically engineered bacteria are capable of producing one or more immune modulators in combination with one or more viral, bacterial, fungal, or cancer protein. In one embodiment, the subject to which the bacteria are delivered generate and sustain an immune response against the one or more viral, bacterial, fungal, or cancer protein, thereby preventing and/or treating the viral, bacterial, or fungal infection or cancer in the subject.

[0126] In some aspects, the disclosure provides a genetically engineered microorganism that is capable of delivering one or more effector molecules, e.g., immune modulators, such as immune initiators and/or immune sustainers. In some aspects, the disclosure relates to a genetically engineered microorganism that is delivered systemically, e.g., via any of the delivery means described in the present disclosure, and are capable of producing one or more effector molecules, e.g., immune initiators and/or immune sustainers, as described herein. In some aspects, the disclosure relates to a genetically engineered microorganism that is delivered locally, and are capable of producing one or more effector molecules, e.g., immune initiators and/or immune sustainers. In some aspects, the compositions and methods disclosed herein may be used to deliver one or more effector molecules, e.g., immune initiators and/or immune sustainers selectively, thereby reducing systemic cytotoxicity or systemic immune dysfunction, e.g., the onset of an autoimmune event or other immune-related adverse event.

[0127] In some aspects, disclosed here is a recombinant microorganism capable of displaying a protein, e.g., an antigen. In one embodiment, the recombinant microorganism express a display protein. In one aspect, the display protein comprises an anchor domain, e.g., intimin, PelB-PAL, YiaT, LppOmpA, BAN, OmsY, Invasin, IgA, PgsA, Ice nucleation protein, and NGIgAsig-NGIgAb, a linker, and a displayed protein, e.g., antigen.

[0128] In order that the disclosure may be more readily understood, certain terms are first defined. These definitions should be read in light of the remainder of the disclosure and as understood by a person of ordinary skill in the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art. Additional definitions are set forth throughout the detailed description.

[0129] As used herein, the term "microbial," refers to or related to a microorganism, e.g., a virus, a bacterium, and a fungi.

[0130] As used herein, the term "display protein" refers to a protein, e.g., a fusion protein, which comprises an anchor domain, a linker, and a displayed protein. As a non-limiting example of a display protein, see, for example, FIG. 1.

[0131] As used herein, the term "anchor domain" refers to a protein capable of anchoring a displayed protein to the outer membrane of a microorganism, e.g., recombinant bacterium. Anchor domains are well known to those of ordinary skill in the art and include, for example, Intimin, PAL, PelB-PAL, YiaT, BclA, LppOmpA, BAN, OmsY, Invasin, IgA, PgsA, Ice nucleation protein (INP), and NGIgAsig-NGIgAb.

[0132] LppOmpA is described, for example, in Francisco et al., Proc. Natl. Acad. Sci. USA 89:2713-2717, 1992; and Francisco et al., Proc. Natl. Acad. Sci. USA, 90:10444-10448, 1993; the entire contents of each of which are expressly incorporated herein by reference. LppOmpA comprises the Lpp signal peptide and first 9 amino acids-Gly-Ile-OmpA. Peptidoglycan-associated lipoprotein (PAL) is described at least in Dhillon et al., Letters in Applied Microbiology, 28:350-354, 1999, the entire contents of which are expressly incorporated herein by reference. NGIgA is described a least in Pyo et al., Vaccine, 27(14):2030-2036, 2009, the entire contents of which are expressly incorporated herein by reference. Ice nucleation protein (INP) is described in Li et al., FEMS Microbiology Letters, 299(1):44-52, 2009, the entire contents of which are expressly incorporated herein by reference. BclA is described at least in Park et al., Microbial Cell Factories, 12, article 81, 2013, the entire contents of which are expressly incorporated herein by reference. Intimin is described at least in Wentzel et al., J. Bacteriol., 183(24):7273-7284, 2001, the entire contents of which are expressly incorporated herein by reference.

[0133] As used herein the term "linker" refers to a protein used to fuse the anchor domain to the displayed protein. In one embodiment, a linker protein comprises an AB epitope, such as FLAG or HIS tags, Linker proteins are well known to those of ordinary skill in the art and include, for example, GGGGS (SEQ ID NO: 1477), (GGGGS)x2 (SEQ ID NO: 1478), (GGGGS)x3 (SEQ ID NO: 1479), EAAAK (SEQ ID NO: 1480), (EAAAK)x2 (SEQ ID NO: 1481), (EAAAK)x3 (SEQ ID NO: 1482), etc.

[0134] As used herein, the term "displayed protein" refers to a protein which can be displayed on the surface of a recombinant bacterium. In one embodiment, a displayed protein can be a reporter protein, e.g., GFP. In another embodiment, a displayed protein can be a protein which is capable of inducing an immune response in a subject, e.g., a human subject. In one embodiment, the displayed protein can be a microbial protein, e.g., a viral protein, a bacterial protein, or a fungal protein. In one embodiment, the displayed protein can be a cancer protein. In one embodiment, the viral protein can be a coronavirus protein. In another embodiment, the protein can be the nanobody A4, which is recognized by CD47-IgG. In one embodiment, the displayed protein is an antigen.

[0135] As used herein, the term "antigen" refers to molecular structure, e.g., a protein, which is recognized by host B-cell receptor or host T cell-receptor and capable of inducing immune response in a subject.

[0136] As used herein, the term "coronavirus," ("CoV"; subfamily Coronavirinae, family Coronaviridae, order Nidovirales), refers to a group of highly diverse, enveloped, positive-sense, single-stranded RNA viruses that cause respiratory, enteric, hepatic and neurological diseases of varying severity in a broad range of animal species, including humans. Coronaviruses are subdivided into four genera: Alphacoronavirus, Betacoronavirus (13CoV), Gammacoronavirus and Deltacoronavirus.

[0137] Any coronavirus that infects humans and animals is encompassed by the term "coronavirus" as used herein. Exemplary coronaviruses encompassed by the term include the coronaviruses that cause a common cold-like respiratory illness, e.g., human coronavirus 229E (HCoV-229E), human coronavirus NL63 (HCoV-NL63), human coronavirus OC43 (HCoV-OC43), and human coronavirus HKU1 (HCoV-HKU1); the coronavirus that causes avian infectious bronchitis virus (IBV); the coronavirus that causes murine hepatitis virus (MHV); the coronavirus that causes porcine transmissible gastroenteritis virus PRCoV; the coronavirus that causes porcine respiratory coronavirus and bovine coronavirus; the coronavirus that causes Severe Acute Respiratory Syndrome (SARS), the coronavirus that causes the Middle East respiratory syndrome (MERS), and the coronavirus that causes Severe Acute Respiratory Syndrome 2 (SARS-CoV-2; COVID-19).

[0138] The coronavirus (CoV) genome is a single-stranded, non-segmented RNA genome, which is approximately 26-32 kb. It contains 5-methylated caps and 3'-polyadenylated tails and is arranged in the order of 5', replicase genes, genes encoding structural proteins (spike glycoprotein (S), envelope protein (E), membrane protein (M) and nucleocapsid protein (N)), polyadenylated tail and then the 3' end. The partially overlapping 5-terminal open reading frame 1a/b (ORF1a/b) is within the 5' two-thirds of the CoV genome and encodes the large replicase polyprotein 1a (pp 1a) and pp lab. These polyproteins are cleaved by papain-like cysteine protease (PLpro) and 3C-like serine protease (3CLpro) to produce non-structural proteins, including RNA-dependent RNA polymerase (RdRp) and helicase (Hel), which are important enzymes involved in the transcription and replication of CoVs. The 3' one-third of the CoV genome encodes the structural proteins (S, E, M and N), which are essential for virus-cell-receptor binding and virion assembly, and other non-structural proteins and accessory proteins that may have immunomodulatory effects. (Peiris J S., et al., 2003, Nat. Med. 10 (Suppl. 12): 88-97).

[0139] As a coronavirus is a positive-sense, single-stranded RNA virus having a 5' methylated cap and a 3' polyadenylated tail, once the virus enters the cell and is uncoated, the viral RNA genome attaches to the host cell's ribosome for direct translation. The host ribosome translates the initial overlapping open reading frame of the virus genome and forms a long polyprotein. The polyprotein has its own proteases which cleave the polyprotein into multiple nonstructural proteins.

[0140] A number of the nonstructural proteins coalesce to form a multi-protein replicase-transcriptase complex (RTC). The main replicase-transcriptase protein is the RNA-dependent RNA polymerase (RdRp). It is directly involved in the replication and transcription of RNA from an RNA strand. The other nonstructural proteins in the complex assist in the replication and transcription process. The exoribonuclease non-structural protein for instance provides extra fidelity to replication by providing a proofreading function which the RNA-dependent RNA polymerase lacks.

[0141] One of the main functions of the complex is to replicate the viral genome. RdRp directly mediates the synthesis of negative-sense genomic RNA from the positive-sense genomic RNA. This is followed by the replication of positive-sense genomic RNA from the negative-sense genomic RNA. The other important function of the complex is to transcribe the viral genome. RdRp directly mediates the synthesis of negative-sense subgenomic RNA molecules from the positive-sense genomic RNA. This is followed by the transcription of these negative-sense subgenomic RNA molecules to their corresponding positive-sense mRNAs

[0142] The replicated positive-sense genomic RNA becomes the genome of the progeny viruses.

[0143] As use herein, the terms "severe acute respiratory syndrome coronavirus 2," "SARS-CoV-2," "2019-nCoV," refer to the novel coronavirus that caused a pneumonia outbreak first reported in Wuhan, China in December 2019 ("COVID-19"). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that SARS-CoV-2 was most closely related (89.1% nucleotide similarity similarity) to SARS-CoV.

[0144] The term "SARS-CoV-2," as used herein, also refers to naturally occurring RNA sequence variations of the SARS-CoV-2 genome.

[0145] Additional examples of coronavirus genomes and mRNA sequences are readily available using publicly available databases, e.g., GenBank, UniProt, and OMIM.

[0146] As used herein the term "immune initiation" or "initiating the immune response" refers to advancement through the steps which lead to the generation and establishment of an immune response.

[0147] As used herein the term "immune sustenance" or "sustaining the immune response" refers to the advancement through steps which ensure the immune response is broadened and strengthened over time and which prevent dampening or suppression of the immune response. For example, these steps could include i.e., T cell trafficking, recognition of target cells though TCRs, and overcoming immune suppression, i.e., depletion or inhibition of T regulatory cells and preventing the establishment of other active suppression of the effector response.

[0148] Accordingly, in some embodiments, the genetically engineered bacteria are capable of producing one or more effector molecules, e.g., immune modulators, which modulate, e.g., intensify the initiation of the immune response. Accordingly, in some embodiments, the genetically engineered bacteria are capable of producing one or more effector molecules, e.g., immune modulators, which modulate, e.g., enhance, sustenance of the immune response. Accordingly, in some embodiments, the genetically engineered bacteria are capable of producing one or more effector molecules, e.g., immune modulators, which modulate, e.g., intensify, the initiation of the immune response and one or more one or more effector molecules, e.g., immune modulators, which modulate, e.g., enhance, sustenance of the immune response.

[0149] Accordingly, in some embodiments, the genetically engineered bacteria comprise gene sequences encoding one or more effector molecules, e.g., immune modulators, which modulate, e.g., intensify the initiation of the immune response. Accordingly, in some embodiments, the genetically engineered bacteria comprise gene sequences encoding one or more effector molecules, e.g., immune modulators, which modulate, e.g., enhance, sustenance of the immune response. Accordingly, in some embodiments, the genetically engineered bacteria comprise gene sequences encoding one or more effector molecules, e.g., immune modulators, which modulate, e.g., intensify, the initiation of the immune response and one or more one or more effector molecules, e.g., immune modulators, which modulate, e.g., enhance, sustenance of the immune response.

[0150] An "effector", "effector substance" or "effector molecule" refers to one or more molecules, therapeutic substances, or drugs of interest. In one embodiment, the "effector" is produced by a modified microorganism, e.g., bacteria. In another embodiment, a modified microorganism capable of producing a first effector described herein is administered in combination with a second effector, e.g., a second effector not produced by a modified microorganism but administered before, at the same time as, or after, the administration of the modified microorganism producing the first effector.

[0151] A non-limiting example of such effector or effector molecules are "immune modulators," which include immune sustainers and/or immune initiators as described herein. In some embodiments, the modified microorganism is capable of producing two or more effector molecules or immune modulators. In some embodiments, the modified microorganism is capable of producing three, four, five, six, seven, eight, nine, or ten effector molecules or immune modulators. In some embodiments, the effector molecule or immune modulator is a therapeutic molecule that is useful for preventing and/or treating a viral disease, e.g., the coronavirus disease 2019 (COVID-19). In another embodiment, a modified microorganism capable of producing a first immune modulator described herein is administered in combination with a second immune modulator, e.g., a second immune modulator not produced by a modified microorganism but administered before, at the same time as, or after, the administration of the modified microorganism producing the first immune modulator.

[0152] In some embodiments, the effector or immune modulator is a therapeutic molecule encoded by at least one gene. In other embodiments, the effector or immune modulator is a therapeutic molecule produced by an enzyme encoded by at least one gene. In alternate embodiments, the effector molecule or immune modulator is a therapeutic molecule produced by a biochemical or biosynthetic pathway encoded by at least one gene. In another embodiment, the effector molecule or immune modulator is at least one enzyme of a biochemical, biosynthetic, or catabolic pathway encoded by at least one gene. In some embodiments, the effector molecule or immune modulator may be a nucleic acid molecule that mediates RNA interference, microRNA response or inhibition, TLR response, antisense gene regulation, target protein binding (aptamer or decoy oligos), or gene editing, such as CRISPR interference. Other types of effectors and immune modulators are described and listed herein.

[0153] Non-limiting examples of effector molecules and/or immune modulators include immune checkpoint inhibitors (e.g., CTLA-4 antibodies, PD-1 antibodies, PDL-1 antibodies), cytotoxic agents (e.g., Cly A, FASL, TRAIL, TNF.alpha.), immunostimulatory cytokines and co-stimulatory molecules (e.g., OX40 antibody or OX40L, CD28, ICOS, CCL21, IL-2, IL-18, IL-15, IL-12, IFN-gamma, IL-21, TNFs, GM-CSF), antigens and antibodies (e.g., viral antigens, tumor antigens, neoantigens, CtxB-PSA fusion protein, CPV-OmpA fusion protein, NY-ESO-1 tumor antigen, RAF1, antibodies against immune suppressor molecules, anti-VEGF, Anti-CXR4/CXCL12, anti-GLP1, anti-GLP2, anti-galectin1, anti-galectin3, anti-Tie2, anti-CD47, antibodies against immune checkpoints, antibodies against immunosuppressive cytokines and chemokines), DNA transfer vectors (e.g., endostatin, thrombospondin-1, TRAIL, SMAC, Stat3, Bcl2, FLT3L, GM-CSF, IL-12, AFP, VEGFR2), and enzymes (e.g., E. coli CD, HSV-TK), immune stimulatory metabolites and biosynthetic pathway enzymes that produce them (STING agonists, e.g., c-di-AMP, 3'3'-cGAMP, and 2'3'-cGAMP; arginine, tryptophan).

[0154] Immune modulators include, inter alia, immune initiators and immune sustainers.

[0155] As used herein, the term "immune initiator" or "initiator" refers to a class of effectors or molecules, e.g., immune modulators, or substances. In one embodiment, an immune initiator may be produced by a modified microorganism, e.g., bacterium, described herein, or may be administered in combination with a modified microorganism of the disclosure. For example, a modified microorganism capable of producing a first immune initiator or immune sustainer described herein is administered in combination with a second immune initiator, e.g., a second immune initiator not produced by a modified microorganism but administered before, at the same time as, or after, the administration of the modified microorganism producing the first immune initiator or immune sustainer. Non-limiting examples of such immune initiators are described in further detail herein.

[0156] In some embodiments, an immune initiator is a therapeutic molecule encoded by at least one gene. Non-limiting examples of such therapeutic molecules are described herein and include, but are not limited to, cytokines, chemokines, single chain antibodies (agonistic or antagonistic), ligands (agonistic or antagonistic), co-stimulatory receptors/ligands and the like. In another embodiment, an immune initiator is a therapeutic molecule produced by an enzyme encoded by at least one gene. Non-limiting examples of such enzymes are described herein and include, but are not limited to, DacA and cGAS, which produce a STING agonist. In another embodiment, an immune initiator is at least one enzyme of a biosynthetic pathway encoded by at least one gene. Non-limiting examples of such biosynthetic pathways are described herein and include, but are not limited to, enzymes involved in the production of arginine. In another embodiment, an immune initiator is at least one enzyme of a catabolic pathway encoded by at least one gene. Non-limiting examples of such catabolic pathways are described herein and include, but are not limited to, enzymes involved in the catabolism of a harmful metabolite. In another embodiment, an immune initiator is at least one molecule produced by at least one enzyme of a biosynthetic pathway encoded by at least one gene. In another embodiment, an immune initiator is a therapeutic molecule produced by metabolic conversion, i.e., the immune initiator is a metabolic converter. In other embodiments, the immune initiator may be a nucleic acid molecule that mediates RNA interference, microRNA response or inhibition, TLR response, antisense gene regulation, target protein binding (aptamer or decoy oligos), gene editing, such as CRISPR interference.

[0157] The term "immune initiator" may also refer to any modifications, such as mutations or deletions, in endogenous genes. In some embodiments, the bacterium is engineered to express the biochemical, biosynthetic, or catabolic pathway. In some embodiments, the bacterium is engineered to produce a second messenger molecule.

[0158] As used herein, the term "low oxygen" is meant to refer to a level, amount, or concentration of oxygen (O.sub.2) that is lower than the level, amount, or concentration of oxygen that is present in the atmosphere (e.g., <21% O.sub.2; <160 torr O.sub.2)). Thus, the term "low oxygen condition or conditions" or "low oxygen environment" refers to conditions or environments containing lower levels of oxygen than are present in the atmosphere.

[0159] In some embodiments, the term "low oxygen" is meant to refer to the level, amount, or concentration of oxygen (O.sub.2) found in a mammalian gut, e.g., lumen, stomach, small intestine, duodenum, jejunum, ileum, large intestine, cecum, colon, distal sigmoid colon, rectum, and anal canal. In some embodiments, the term "low oxygen" is meant to refer to a level, amount, or concentration of O.sub.2 that is 0-60 mmHg O.sub.2 (0-60 torr O.sub.2) (e.g., 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, and 60 mmHg O.sub.2), including any and all incremental fraction(s) thereof (e.g., 0.2 mmHg, 0.5 mmHg O.sub.2, 0.75 mmHg O.sub.2, 1.25 mmHg O.sub.2, 2.175 mmHg O.sub.2, 3.45 mmHg 02, 3.75 mmHg 02, 4.5 mmHg 02, 6.8 mmHg 02, 11.35 mmHg 02, 46.3 mmHg O.sub.2, 58.75 mmHg, etc., which exemplary fractions are listed here for illustrative purposes and not meant to be limiting in any way). In some embodiments, "low oxygen" refers to about 60 mmHg O.sub.2 or less (e.g., 0 to about 60 mmHg O.sub.2). The term "low oxygen" may also refer to a range of O.sub.2 levels, amounts, or concentrations between 0-60 mmHg O.sub.2 (inclusive), e.g., 0-5 mmHg O.sub.2, <1.5 mmHg O.sub.2, 6-10 mmHg, <8 mmHg, 47-60 mmHg, etc. which listed exemplary ranges are listed here for illustrative purposes and not meant to be limiting in any way. See, for example, Albenberg et al., Gastroenterology, 147(5): 1055-1063 (2014); Bergofsky et al., J Clin. Invest., 41(11): 1971-1980 (1962); Crompton et al., J Exp. Biol., 43: 473-478 (1965); He et al., PNAS (USA), 96: 4586-4591 (1999); McKeown, Br. J. Radiol., 87:20130676 (2014) (doi: 10.1259/brj.20130676), each of which discusses the oxygen levels found in the mammalian gut of various species and each of which are incorporated by reference herewith in their entireties.

[0160] In some embodiments, the term "low oxygen" is meant to refer to the level, amount, or concentration of oxygen (O.sub.2) found in a mammalian organ or tissue other than the gut, e.g., urogenital tract, tumor tissue, etc. in which oxygen is present at a reduced level, e.g., at a hypoxic or anoxic level. In some embodiments, "low oxygen" is meant to refer to the level, amount, or concentration of oxygen (O.sub.2) present in partially aerobic, semi aerobic, microaerobic, nonaerobic, microoxic, hypoxic, anoxic, and/or anaerobic conditions. For example, Table 1 summarizes the amount of oxygen present in various organs and tissues. In some embodiments, the level, amount, or concentration of oxygen (O.sub.2) is expressed as the amount of dissolved oxygen ("DO") which refers to the level of free, non-compound oxygen (O.sub.2) present in liquids and is typically reported in milligrams per liter (mg/L), parts per million (ppm; 1 mg/L=1 ppm), or in micromoles (umole) (1 umole O.sub.2=0.022391 mg/L O.sub.2). Fondriest Environmental, Inc., "Dissolved Oxygen", Fundamentals of Environmental Measurements, 19 Nov. 2013, www.fondriest.com/environmental-measurements/parameters/water-quality/dis- solved-oxygen/>.

[0161] In some embodiments, the term "low oxygen" is meant to refer to a level, amount, or concentration of oxygen (O.sub.2) that is about 6.0 mg/L DO or less, e.g., 6.0 mg/L, 5.0 mg/L, 4.0 mg/L, 3.0 mg/L, 2.0 mg/L, 1.0 mg/L, or 0 mg/L, and any fraction therein, e.g., 3.25 mg/L, 2.5 mg/L, 1.75 mg/L, 1.5 mg/L, 1.25 mg/L, 0.9 mg/L, 0.8 mg/L, 0.7 mg/L, 0.6 mg/L, 0.5 mg/L, 0.4 mg/L, 0.3 mg/L, 0.2 mg/L and 0.1 mg/L DO, which exemplary fractions are listed here for illustrative purposes and not meant to be limiting in any way. The level of oxygen in a liquid or solution may also be reported as a percentage of air saturation or as a percentage of oxygen saturation (the ratio of the concentration of dissolved oxygen (O.sub.2) in the solution to the maximum amount of oxygen that will dissolve in the solution at a certain temperature, pressure, and salinity under stable equilibrium). Well-aerated solutions (e.g., solutions subjected to mixing and/or stirring) without oxygen producers or consumers are 100% air saturated.

[0162] In some embodiments, the term "low oxygen" is meant to refer to 40% air saturation or less, e.g., 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, 29%, 28%, 27%, 26%, 25%, 24%, 23%, 22%, 21%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, and 0% air saturation, including any and all incremental fraction(s) thereof (e.g., 30.25%, 22.70%, 15.5%, 7.7%, 5.0%, 2.8%, 2.0%, 1.65%, 1.0%, 0.9%, 0.8%, 0.75%, 0.68%, 0.5%. 0.44%, 0.3%, 0.25%, 0.2%, 0.1%, 0.08%, 0.075%, 0.058%, 0.04%. 0.032%, 0.025%, 0.01%, etc.) and any range of air saturation levels between 0-40%, inclusive (e.g., 0-5%, 0.05-0.1%, 0.1-0.2%, 0.1-0.5%, 0.5-2.0%, 0-10%, 5-10%, 10-15%, 15-20%, 20-25%, 25-30%, etc.).

[0163] The exemplary fractions and ranges listed here are for illustrative purposes and not meant to be limiting in any way. In some embodiments, the term "low oxygen" is meant to refer to 9% O.sub.2 saturation or less, e.g., 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0%, O.sub.2 saturation, including any and all incremental fraction(s) thereof (e.g., 6.5%, 5.0%, 2.2%, 1.7%, 1.4%, 0.9%, 0.8%, 0.75%, 0.68%, 0.5%. 0.44%, 0.3%, 0.25%, 0.2%, 0.1%, 0.08%, 0.075%, 0.058%, 0.04%. 0.032%, 0.025%, 0.01%, etc.) and any range of O.sub.2 saturation levels between 0-9%, inclusive (e.g., 0-5%, 0.05-0.1%, 0.1-0.2%, 0.1-0.5%, 0.5-2.0%, 0-8%, 5-7%, 0.3-4.2% O.sub.2, etc.). The exemplary fractions and ranges listed here are for illustrative purposes and not meant to be limiting in any way.

TABLE-US-00001 TABLE 1 Oxygen present in various organs and tissues Compartment Oxygen Tension stomach ~60 torr (e.g., 58 +/- 15 torr) duodenum and first ~30 torr (e.g., 32 +/- 8 torr);~20% part of jejunum oxygen in ambient air Ileum (mid-small ~10 torr;~6% oxygen in ambient intestine) air (e.g., 11 +/- 3 torr) Distal sigmoid colon ~3 torr (e.g., 3 +/- 1 torr) colon <2 torr Lumen of cecum <1 torr tumor <32 torr (most tumors are < 15 torr)

[0164] As used herein, the term "gene" or "gene sequence" refers to any sequence expressing a polypeptide or protein, including genomic sequences, cDNA sequences, naturally occurring sequences, artificial sequences, and codon optimized sequences. The term "gene" or "gene sequence" inter alia includes modification of endogenous genes, such as deletions, mutations, and expression of native and non-native genes under the control of a promoter that that they are not normally associated with in nature.

[0165] As used herein the terms "gene cassette" and "circuit" or "circuitry" inter alia refers to any sequence expressing a polypeptide or protein, including genomic sequences, cDNA sequences, naturally occurring sequences, artificial sequences, and codon optimized sequences includes modification of endogenous genes, such as deletions, mutations, and expression of native and non-native genes under the control of a promoter that that they are not normally associated with in nature.

[0166] An antibody generally refers to a polypeptide of the immunoglobulin family or a polypeptide comprising fragments of an immunoglobulin that is capable of noncovalently, reversibly, and in a specific manner binding a corresponding antigen. An exemplary antibody structural unit comprises a tetramer composed of two identical pairs of polypeptide chains, each pair having one "light" (about 25 kD) and one "heavy" chain (about 50-70 kD), connected through a disulfide bond.

[0167] As used herein, the term "antibody" or "antibodies" is meant to encompasses all variations of antibody and fragments thereof that possess one or more particular binding specificities. Thus, the term "antibody" or "antibodies" is meant to include full length antibodies, chimeric antibodies, humanized antibodies, single chain antibodies (ScFv, camelids), Fab, Fab', multimeric versions of these fragments (e.g., F(ab')2), single domain antibodies (sdAB, V.sub.HH framents), heavy chain antibodies (HCAb), nanobodies, diabodies, and minibodies. Antibodies can have more than one binding specificity, e.g. be bispecific. The term "antibody" is also meant to include so-called antibody mimetics, i.e., which can specifically bind antigens but do not have an antibody-related structure.

[0168] A "single-chain antibody" or "single-chain antibodies" typically refers to a peptide comprising a heavy chain of an immunoglobulin, a light chain of an immunoglobulin, and optionally a linker or bond, such as a disulfide bond. The single-chain antibody lacks the constant Fc region found in traditional antibodies. In some embodiments, the single-chain antibody is a naturally occurring single-chain antibody, e.g., a camelid antibody. In some embodiments, the single-chain antibody is a synthetic, engineered, or modified single-chain antibody. In some embodiments, the single-chain antibody is capable of retaining substantially the same antigen specificity as compared to the original immunoglobulin despite the addition of a linker and the removal of the constant regions. In some aspects, the single chain antibody can be a "scFv antibody", which refers to a fusion protein of the variable regions of the heavy (VH) and light chains (VL) of immunoglobulins (without any constant regions), optionally connected with a short linker peptide of ten to about 25 amino acids, as described, for example, in U.S. Pat. No. 4,946,778, the contents of which is herein incorporated by reference in its entirety. The Fv fragment is the smallest fragment that holds a binding site of an antibody, which binding site may, in some aspects, maintain the specificity of the original antibody. Techniques for the production of single chain antibodies are described in U.S. Pat. No. 4,946,778.

[0169] As used herein, the term "polypeptide" includes "polypeptide" as well as "polypeptides," and refers to a molecule composed of amino acid monomers linearly linked by amide bonds (i.e., peptide bonds). The term "polypeptide" refers to any chain or chains of two or more amino acids, and does not refer to a specific length of the product. Thus, "peptides," "dipeptides," "tripeptides, "oligopeptides," "protein," "amino acid chain," or any other term used to refer to a chain or chains of two or more amino acids, are included within the definition of "polypeptide," and the term "polypeptide" may be used instead of, or interchangeably with any of these terms. The term "polypeptide" is also intended to refer to the products of post-expression modifications of the polypeptide, including but not limited to glycosylation, acetylation, phosphorylation, amidation, derivatization, proteolytic cleavage, or modification by non-naturally occurring amino acids. In some embodiments, the polypeptide is produced by the genetically engineered bacteria of the current invention. A polypeptide of the invention may be of a size of about 3 or more, 5 or more, 10 or more, 20 or more, 25 or more, 50 or more, 75 or more, 100 or more, 200 or more, 500 or more, 1,000 or more, or 2,000 or more amino acids.

[0170] An "isolated" polypeptide or a fragment, variant, or derivative thereof refers to a polypeptide that is not in its natural milieu. No particular level of purification is required. Recombinantly produced polypeptides and proteins expressed in host cells, including but not limited to bacterial or mammalian cells, are considered isolated for purposed of the invention, as are native or recombinant polypeptides which have been separated, fractionated, or partially or substantially purified by any suitable technique. Recombinant peptides, polypeptides or proteins refer to peptides, polypeptides or proteins produced by recombinant DNA techniques, i.e. produced from cells, microbial or mammalian, transformed by an exogenous recombinant DNA expression construct encoding the polypeptide. Proteins or peptides expressed in most bacterial cultures will typically be free of glycan. Fragments, derivatives, analogs or variants of the foregoing polypeptides, and any combination thereof are also included as polypeptides. The terms "fragment," "variant," "derivative" and "analog" include polypeptides having an amino acid sequence sufficiently similar to the amino acid sequence of the original peptide and include any polypeptides, which retain at least one or more properties of the corresponding original polypeptide. Fragments of polypeptides of the present invention include proteolytic fragments, as well as deletion fragments. Fragments also include specific antibody or bioactive fragments or immunologically active fragments derived from any polypeptides described herein. Variants may occur naturally or be non-naturally occurring. Non-naturally occurring variants may be produced using mutagenesis methods known in the art. Variant polypeptides may comprise conservative or non-conservative amino acid substitutions, deletions or additions.

[0171] Polypeptides also include fusion proteins. As used herein, the term "variant" includes a fusion protein, which comprises a sequence of the original peptide or sufficiently similar to the original peptide. As used herein, the term "fusion protein" refers to a chimeric protein comprising amino acid sequences of two or more different proteins. Typically, fusion proteins result from well known in vitro recombination techniques. Fusion proteins may have a similar structural function (but not necessarily to the same extent), and/or similar regulatory function (but not necessarily to the same extent), and/or similar biochemical function (but not necessarily to the same extent) and/or immunological activity (but not necessarily to the same extent) as the individual original proteins which are the components of the fusion proteins. "Derivatives" include but are not limited to peptides, which contain one or more naturally occurring amino acid derivatives of the twenty standard amino acids. "Similarity" between two peptides is determined by comparing the amino acid sequence of one peptide to the sequence of a second peptide. An amino acid of one peptide is similar to the corresponding amino acid of a second peptide if it is identical or a conservative amino acid substitution. Conservative substitutions include those described in Dayhoff, M. O., ed., The Atlas of Protein Sequence and Structure 5, National Biomedical Research Foundation, Washington, D.C. (1978), and in Argos, EMBO J. 8 (1989), 779-785. For example, amino acids belonging to one of the following groups represent conservative changes or substitutions: Ala, Pro, Gly, Gln, Asn, Ser, Thr; Cys, Ser, Tyr, Thr; Val, Ile, Leu, Met, Ala, Phe; Lys, Arg, His; Phe, Tyr, Trp, His; and Asp, Glu.

[0172] As used herein, the term "sufficiently similar" means a first amino acid sequence that contains a sufficient or minimum number of identical or equivalent amino acid residues relative to a second amino acid sequence such that the first and second amino acid sequences have a common structural domain and/or common functional activity. For example, amino acid sequences that comprise a common structural domain that is at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100%, identical are defined herein as sufficiently similar. Preferably, variants will be sufficiently similar to the amino acid sequence of the peptides of the invention. Such variants generally retain the functional activity of the peptides of the present invention. Variants include peptides that differ in amino acid sequence from the native and wt peptide, respectively, by way of one or more amino acid deletion(s), addition(s), and/or substitution(s). These may be naturally occurring variants as well as artificially designed ones.

[0173] As used herein the term "linker", "linker peptide" or "peptide linkers" or "linker" refers to synthetic or non-native or non-naturally-occurring amino acid sequences that connect or link two polypeptide sequences, e.g., that link two polypeptide domains. As used herein the term "synthetic" refers to amino acid sequences that are not naturally occurring. Exemplary linkers are described herein. Additional exemplary linkers are provided in US 20140079701, the contents of which are herein incorporated by reference in its entirety. In some embodiments, the linker is a glycine rich linker. In some embodiments, the linker is (Gly-Gly-Gly-Gly-Ser)n (SEQ ID NO: 1507). In some embodiments, the linker comprises SEQ ID NO: 979.

[0174] As used herein the term "codon-optimized sequence" refers to a sequence, which was modified from an existing coding sequence, or designed, for example, to improve translation in an expression host cell or organism of a transcript RNA molecule transcribed from the coding sequence, or to improve transcription of a coding sequence. Codon optimization includes, but is not limited to, processes including selecting codons for the coding sequence to suit the codon preference of the expression host organism.

[0175] Many organisms display a bias or preference for use of particular codons to code for insertion of a particular amino acid in a growing polypeptide chain. Codon preference or codon bias, differences in codon usage between organisms, is allowed by the degeneracy of the genetic code, and is well documented among many organisms. Codon bias often correlates with the efficiency of translation of messenger RNA (mRNA), which is in turn believed to be dependent on, inter alia, the properties of the codons being translated and the availability of particular transfer RNA (tRNA) molecules. The predominance of selected tRNAs in a cell is generally a reflection of the codons used most frequently in peptide synthesis. Accordingly, genes can be tailored for optimal gene expression in a given organism based on codon optimization.

[0176] As used herein, the terms "secretion system" or "secretion protein" refers to a native or non-native secretion mechanism capable of secreting or exporting the immune modulator from the microbial, e.g., bacterial cytoplasm. Non-limiting examples of secretion systems for gram negative bacteria include the modified type III flagellar, type I (e.g., hemolysin secretion system), type II, type IV, type V, type VI, and type VII secretion systems, resistance-nodulation-division (RND) multi-drug efflux pumps, various single membrane secretion systems. Non-limiting examples of secretion systems are described herein.

[0177] As used herein, the term "transporter" is meant to refer to a mechanism, e.g., protein or proteins, for importing a molecule into the microorganism from the extracellular milieu.

[0178] The immune system is typically most broadly divided into two categories--innate immunity and adaptive immunity--although the immune responses associated with these immunities are not mutually exclusive. "Innate immunity" refers to non-specific defense mechanisms that are activated immediately or within hours of a foreign agent's or antigen's appearance in the body. These mechanisms include physical barriers such as skin, chemicals in the blood, and immune system cells, such as dendritic cells (DCs), leukocytes, phagocytes, macrophages, neutrophils, and natural killer cells (NKs), that attack foreign agents or cells in the body and alter the rest of the immune system to the presence of the foreign agents. During an innate immune response, cytokines and chemokines are produced which in combination with the presentation of immunological antigens, work to activate adaptive immune cells and initiate a full blown immunologic response. "Adaptive immunity" or "acquired immunity" refers to antigen-specific immune response. The antigen must first be processed or presented by antigen presenting cells (APCs). An antigen-presenting cell or accessory cell is a cell that displays antigens directly or complexed with major histocompatibility complexes (MHCs) on their surfaces. Professional antigen-presenting cells, including macrophages, B cells, and dendritic cells, specialize in presenting foreign antigen to T helper cells in a MHC-II restricted manner, while other cell types can present antigen originating inside the cell to cytotoxic T cells in a MHC-I restricted manner. Once an antigen has been presented and recognized, the adaptive immune system activates an army of immune cells specifically designed to attack that antigen. Like the innate system, the adaptive system includes both humoral immunity components (B lymphocyte cells) and cell-mediated immunity (T lymphocyte cells) components. B cells are activated to secrete antibodies, which travel through the bloodstream and bind to the foreign antigen. Helper T cells (regulatory T cells, CD4+ cells) and cytotoxic T cells (CTL, CD8+ cells) are activated when their T cell receptor interacts with an antigen-bound MHC molecule. Cytokines and co-stimulatory molecules help the T cells mature, which mature cells, in turn, produce cytokines which allows the production of priming and expansion of additional T cells sustaining the response. Once activated, the helper T cells release cytokines which regulate and direct the activity of different immune cell types, including APCs, macrophages, neutrophils, and other lymphocytes, to kill and remove targeted cells. Helper T cells also secrete extra signals that assist in the activation of cytotoxic T cells which also help to sustain the immune response. Upon activation, CTL undergoes clonal selection, in which it gains functions, divides rapidly to produce an army of activated effector cells, and forms long-lived memory T cells ready to rapidly respond to future threats. Activated CTL then travels throughout the body searching for cells that bear that unique MHC Class I and antigen. The effector CTLs release cytotoxins that form pores in the target cell's plasma membrane, causing apoptosis. Adaptive immunity also includes a "memory" that makes future responses against a specific antigen more efficient. Upon resolution of the infection, T helper cells and cytotoxic T cells die and are cleared away by phagocytes, however, a few of these cells remain as memory cells. If the same antigen is encountered at a later time, these memory cells quickly differentiate into effector cells, shortening the time required to mount an effective response.

[0179] An "immune checkpoint inhibitor" or "immune checkpoint" refers to a molecule that completely or partially reduces, inhibits, interferes with, or modulates one or more immune checkpoint proteins. Immune checkpoint proteins regulate T-cell activation or function, and are known in the art. Non-limiting examples include CTLA-4 and its ligands CD 80 and CD86, and PD-1 and its ligands PD-L1 and PD-L2. Immune checkpoint proteins are responsible for co-stimulatory or inhibitory interactions of T-cell responses, and regulate and maintain self-tolerance and physiological immune responses.

[0180] A "co-stimulatory" molecule or "co-stimulator" is an immune modulator that increase or activates a signal that stimulates an immune response or inflammatory response.

[0181] Examples of bacteria suitable for the methods and compositions in the present invention include, but are not limited to, Bifidobacterium, Caulobacter, Clostridium, Escherichia coli, Listeria, Mycobacterium, Salmonella, Streptococcus, and Vibrio, e.g., Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium breve UCC2003, Bifidobacterium infantis, Bifidobacterium longum, Clostridium acetobutylicum, Clostridium butyricum, Clostridium butyricum M-55, Clostridium butyricum miyairi, Clostridium cochlearum, Clostridium felsineum, Clostridium histolyticum, Clostridium multifermentans, Clostridium novyi-NT, Clostridium paraputrificum, Clostridium pasteureanum, Clostridium pectinovorum, Clostridium perfringens, Clostridium roseum, Clostridium sporogenes, Clostridium tertium, Clostridium tetani, Clostridium tyrobutyricum, Corynebacterium parvum, Escherichia coli MG1655, Escherichia coli Nissle 1917, Listeria monocytogenes, Mycobacterium bovis, Salmonella choleraesuis, Salmonella typhimurium, and Vibrio cholera (Cronin et al., 2012; Forbes, 2006; Jain and Forbes, 2001; Liu et al., 2014; Morrissey et al., 2010; Nuno et al., 2013; Patyar et al., 2010; Cronin, et al., Mol Ther 2010; 18:1397-407).

[0182] "Microorganism" refers to an organism or microbe of microscopic, submicroscopic, or ultramicroscopic size that typically consists of a single cell. Examples of microorganisms include bacteria, viruses, parasites, fungi, certain algae, protozoa, and yeast. In some aspects, the microorganism is modified ("modified microorganism") from its native state to produce one or more effectors or immune modulators. In certain embodiments, the modified microorganism is a modified bacterium. In some embodiments, the modified microorganism is a genetically engineered bacterium. In certain embodiments, the modified microorganism is a modified yeast. In other embodiments, the modified microorganism is a genetically engineered yeast.

[0183] As used herein, the term "recombinant microorganism" refers to a microorganism, e.g., bacterial, yeast, or viral cell, or bacteria, yeast, or virus, that has been genetically modified from its native state. Thus, a "recombinant bacterial cell" or "recombinant bacteria" refers to a bacterial cell or bacteria that have been genetically modified from their native state. For instance, a recombinant bacterial cell may have nucleotide insertions, nucleotide deletions, nucleotide rearrangements, and nucleotide modifications introduced into their DNA. These genetic modifications may be present in the chromosome of the bacteria or bacterial cell, or on a plasmid in the bacteria or bacterial cell. Recombinant bacterial cells disclosed herein may comprise exogenous nucleotide sequences on plasmids. Alternatively, recombinant bacterial cells may comprise exogenous nucleotide sequences stably incorporated into their chromosome.

[0184] A "programmed or engineered microorganism" refers to a microorganism, e.g., bacterial, yeast, or viral cell, or bacteria, yeast, or virus, that has been genetically modified from its native state to perform a specific function. Thus, a "programmed or engineered bacterial cell" or "programmed or engineered bacteria" refers to a bacterial cell or bacteria that has been genetically modified from its native state to perform a specific function. In certain embodiments, the programmed or engineered bacterial cell has been modified to express one or more proteins, for example, one or more proteins that have a therapeutic activity or serve a therapeutic purpose. The programmed or engineered bacterial cell may additionally have the ability to stop growing or to destroy itself once the protein(s) of interest have been expressed.

[0185] "Non-pathogenic bacteria" refer to bacteria that are not capable of causing disease or harmful responses in a host. In some embodiments, non-pathogenic bacteria are Gram-negative bacteria. In some embodiments, non-pathogenic bacteria are Gram-positive bacteria. In some embodiments, non-pathogenic bacteria do not contain lipopolysaccharides (LPS). In some embodiments, non-pathogenic bacteria are commensal bacteria. Examples of non-pathogenic bacteria include, but are not limited to certain strains belonging to the genus Bacillus, Bacteroides, Bifidobacterium, Brevibacteria, Clostridium, Enterococcus, Escherichia coli, Lactobacillus, Lactococcus, Saccharomyces, and Staphylococcus, e.g., Bacillus coagulans, Bacillus subtilis, Bacteroides fragilis, Bacteroides subtilis, Bacteroides thetaiotaomicron, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium lactis, Bifidobacterium longum, Clostridium butyricum, Enterococcus faecium, Escherichia coli Nissle, Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus johnsonii, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactococcus lactis, and Saccharomyces boulardii (Sonnenborn et al., 2009; Dinleyici et al., 2014; U.S. Pat. Nos. 6,835,376; 6,203,797; 5,589,168; 7,731,976). Naturally pathogenic bacteria may be genetically engineered to provide reduce or eliminate pathogenicity.

[0186] "Probiotic" is used to refer to live, non-pathogenic microorganisms, e.g., bacteria, which can confer health benefits to a host organism that contains an appropriate amount of the microorganism. In some embodiments, the host organism is a mammal. In some embodiments, the host organism is a human. In some embodiments, the probiotic bacteria are Gram-negative bacteria. In some embodiments, the probiotic bacteria are Gram-positive bacteria. Some species, strains, and/or subtypes of non-pathogenic bacteria are currently recognized as probiotic bacteria. Examples of probiotic bacteria include, but are not limited to certain strains belonging to the genus Bifidobacteria, Escherichia coli, Lactobacillus, and Saccharomyces, e.g., Bifidobacterium bifidum, Enterococcus faecium, Escherichia coli strain Nissle, Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus paracasei, Lactobacillus plantarum, and Saccharomyces boulardii (Dinleyici et al., 2014; U.S. Pat. Nos. 5,589,168; 6,203,797; 6,835,376). The probiotic may be a variant or a mutant strain of bacterium (Arthur et al., 2012; Cuevas-Ramos et al., 2010; Olier et al., 2012; Nougayrede et al., 2006). Non-pathogenic bacteria may be genetically engineered to enhance or improve desired biological properties, e.g., survivability. Non-pathogenic bacteria may be genetically engineered to provide probiotic properties. Probiotic bacteria may be genetically engineered or programmed to enhance or improve probiotic properties.

[0187] "Operably linked" refers a nucleic acid sequence, e.g., a gene encoding an enzyme for the production of a STING agonist, e.g., a diadenylate cyclase or a c-di-GAMP synthase, that is joined to a regulatory region sequence in a manner which allows expression of the nucleic acid sequence, e.g., acts in cis. A regulatory region is a nucleic acid that can direct transcription of a gene of interest and may comprise promoter sequences, enhancer sequences, response elements, protein recognition sites, inducible elements, promoter control elements, protein binding sequences, 5' and 3' untranslated regions, transcriptional start sites, termination sequences, polyadenylation sequences, and introns.

[0188] An "inducible promoter" refers to a regulatory region that is operably linked to one or more genes, wherein expression of the gene(s) is increased in the presence of an inducer of said regulatory region.

[0189] "Exogenous environmental condition(s)" refer to setting(s) or circumstance(s) under which the promoter described herein is induced. The phrase "exogenous environmental conditions" is meant to refer to the environmental conditions external to the intact (unlysed) engineered microorganism, but endogenous or native to environment or the host subject environment. Thus, "exogenous" and "endogenous" may be used interchangeably to refer to environmental conditions in which the environmental conditions are endogenous to a mammalian body, but external or exogenous to an intact microorganism cell. In some embodiments, the exogenous environmental conditions are low-oxygen, microaerobic, or anaerobic conditions, such as hypoxic and/or necrotic tissues. In some embodiments, the genetically engineered microorganism of the disclosure comprise an oxygen level-dependent promoter. In some aspects, bacteria have evolved transcription factors that are capable of sensing oxygen levels. Different signaling pathways may be triggered by different oxygen levels and occur with different kinetics. An "oxygen level-dependent promoter" or "oxygen level-dependent regulatory region" refers to a nucleic acid sequence to which one or more oxygen level-sensing transcription factors is capable of binding, wherein the binding and/or activation of the corresponding transcription factor activates downstream gene expression.

[0190] Examples of oxygen level-dependent transcription factors include, but are not limited to, FNR (fumarate and nitrate reductase), ANR, and DNR. Corresponding FNR-responsive promoters, ANR (anaerobic nitrate respiration)-responsive promoters, and DNR (dissimilatory nitrate respiration regulator)-responsive promoters are known in the art (see, e.g., Castiglione et al., 2009; Eiglmeier et al., 1989; Galimand et al., 1991; Hasegawa et al., 1998; Hoeren et al., 1993; Salmon et al., 2003), and non-limiting examples are shown in Table 2.

[0191] In a non-limiting example, a promoter (PfnrS) was derived from the E. coli Nissle fumarate and nitrate reductase gene S (fnrS) that is known to be highly expressed under conditions of low or no environmental oxygen (Durand and Storz, 2010; Boysen et al, 2010). The PfnrS promoter is activated under anaerobic conditions by the global transcriptional regulator FNR that is naturally found in Nissle. Under anaerobic conditions, FNR forms a dimer and binds to specific sequences in the promoters of specific genes under its control, thereby activating their expression. However, under aerobic conditions, oxygen reacts with iron-sulfur clusters in FNR dimers and converts them to an inactive form. In this way, the PfnrS inducible promoter is adopted to modulate the expression of proteins or RNA. PfnrS is used interchangeably in this application as FNRS, fnrs, FNR, P-FNRS promoter and other such related designations to indicate the promoter PfnrS.

TABLE-US-00002 TABLE 2 Examples of transcription factors and responsive genes and regulatory regions Transcription Examples of responsive genes, promoters, Factor and/or regulatory regions: FNR nirB, ydfZ, pdhR, focA, ndH, hlyE, narK, narX, narG, yfiD, tdcD ANR arcDABC DNR norb, norC

[0192] As used herein, a "non-native" nucleic acid sequence refers to a nucleic acid sequence not normally present in a microorganism, e.g., an extra copy of an endogenous sequence, or a heterologous sequence such as a sequence from a different species, strain, or substrain of bacteria or virus, or a sequence that is modified and/or mutated as compared to the unmodified sequence from bacteria or virus of the same subtype. In some embodiments, the non-native nucleic acid sequence is a synthetic, non-naturally occurring sequence (see, e.g., Purcell et al., 2013). The non-native nucleic acid sequence may be a regulatory region, a promoter, a gene, and/or one or more genes in gene cassette. In some embodiments, "non-native" refers to two or more nucleic acid sequences that are not found in the same relationship to each other in nature. The non-native nucleic acid sequence may be present on a plasmid or chromosome. In some embodiments, the genetically engineered bacteria of the disclosure comprise a gene that is operably linked to a directly or indirectly inducible promoter that is not associated with said gene in nature, e.g., an FNR-responsive promoter (or other promoter described herein) operably linked to a gene encoding an immune modulator.

[0193] In one embodiment, the effector, or immune modulator, is a therapeutic molecule encoded by at least one non-native gene. In one embodiment, the effector, or immune modulator, is a therapeutic molecule produced by an enzyme encoded by at least one non-native gene. In one embodiment, the effector, or immune modulator, is at least one enzyme of a biosynthetic pathway encoded by at least one non-native gene. In another embodiment, the effector, or immune modulator, is at least one molecule produced by at least one enzyme of a biosynthetic pathway encoded by at least one non-native gene.

[0194] In one embodiment, the immune initiator is a therapeutic molecule encoded by at least one non-native gene. In one embodiment, the immune initiator is a therapeutic molecule produced by an enzyme encoded by at least one non-native gene. In one embodiment, the immune initiator is at least one enzyme of a biosynthetic pathway encoded by at least one non-native gene. In another embodiment, the immune initiator is at least one molecule produced by at least one enzyme of a biosynthetic pathway encoded by at least one non-native gene.

[0195] In one embodiment, the immune sustainer is a therapeutic molecule encoded by at least one non-native gene. In one embodiment, the immune sustainer is a therapeutic molecule produced by an enzyme encoded by at least one non-native gene. In one embodiment, the immune sustainer is at least one enzyme of a biosynthetic pathway encoded by at least one non-native gene. In another embodiment, the immune sustainer is at least one molecule produced by at least one enzyme of a biosynthetic pathway encoded by at least one non-native gene.

[0196] "Constitutive promoter" refers to a promoter that is capable of facilitating continuous transcription of a coding sequence or gene under its control and/or to which it is operably linked. Constitutive promoters and variants are well known in the art and non-limiting examples of constitutive promoters are described herein and in International Patent Application PCT/US2017/013072, filed Jan. 11, 2017 and published as WO2017/123675, the contents of which is herein incorporated by reference in its entirety. In some embodiments, such promoters are active in vitro, e.g., under culture, expansion and/or manufacture conditions. In some embodiments, such promoters are active in vivo, e.g., in conditions found in the in vivo environment, e.g., the gut and/or the microenvironment.

[0197] As used herein, "stably maintained" or "stable" bacterium or virus is used to refer to a bacterial or viral host cell carrying non-native genetic material, e.g., an immune modulator, such that the non-native genetic material is retained, expressed, and propagated. The stable bacterium or virus is capable of survival and/or growth in vitro, e.g., in medium, and/or in vivo, e.g., in hypoxic and/or necrotic tissues. For example, the stable bacterium or virus may be a genetically engineered bacterium comprising non-native genetic material encoding an immune modulator, in which the plasmid or chromosome carrying the non-native genetic material is stably maintained in the bacterium or virus, such that the immune modulator can be expressed in the bacterium or virus, and the bacterium or virus is capable of survival and/or growth in vitro and/or in vivo.

[0198] As used herein, the terms "modulate" and "treat" and their cognates refer to an amelioration of a microbial infection, e.g., the coronavirus disease 2019 (COVID-19), or at least one discernible symptom thereof. In another embodiment, "modulate" and "treat" refer to an amelioration of at least one measurable physical parameter, not necessarily discernible by the patient. For example, the symptoms for patients with COVID-19 vary depending on how serious the infection is. Patients with a mild to moderate upper-respiratory infection may develop symptoms such as runny nose, sneezing, headache, cough, sore throat, fever, or short of breath. In more severe cases, coronavirus infection can cause pneumonia, severe acute respiratory syndrome, kidney failure and even death. Further details regarding signs and symptoms of the various diseases or conditions are provided herein and are well known in the art. In another embodiment, "modulate" and "treat" refer to inhibiting the development of a microbial infection, e.g., COVID-19, either physically (e.g., stabilization of a discernible symptom), physiologically (e.g., stabilization of a physical parameter), or both. In another embodiment, "modulate" and "treat" refer to slowing the development or reversing the development of a microbial infection, e.g., COVID-19. As used herein, "prevent" and its cognates refer to delaying the onset or reducing the risk of acquiring a given disease.

[0199] Those in need of treatment may include individuals already having a particular microbial infection, as well as those at risk of having, or who may ultimately acquire the microbial infection. The need for treatment is assessed, for example, by the presence of one or more risk factors associated with the development of a microbial infection, the presence or progression of a microbial infection, or likely receptiveness to treatment of a subject having the microbial infection.

[0200] Those in need of treatment may include individuals already having a particular viral infection, as well as those at risk of having, or who may ultimately acquire the COVID-19. The need for treatment is assessed, for example, by the presence of one or more risk factors associated with the development of a viral infection, the presence or progression of a viral infection, or likely receptiveness to treatment of a subject having the viral infection.

[0201] As used herein, the term "conventional anti-viral treatment," "conventional anti-viral therapy," "conventional anti-microbial treatment," or "conventional anti-microbial treatment" refers to treatment or therapy that is widely accepted and used by most healthcare professionals. It is different from alternative or complementary therapies, which are not as widely used.

[0202] As used herein a "pharmaceutical composition" refers to a preparation of genetically engineered microorganism of the disclosure with other components such as a physiologically suitable carrier and/or excipient.

[0203] The phrases "physiologically acceptable carrier" and "pharmaceutically acceptable carrier" which may be used interchangeably refer to a carrier or a diluent that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the administered bacterial or viral compound. An adjuvant is included under these phrases.

[0204] The term "excipient" refers to an inert substance added to a pharmaceutical composition to further facilitate administration of an active ingredient. Examples include, but are not limited to, calcium bicarbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, gelatin, vegetable oils, polyethylene glycols, and surfactants, including, for example, polysorbate 20.

[0205] The terms "therapeutically effective dose" and "therapeutically effective amount" are used to refer to an amount of a compound that results in prevention, delay of onset of symptoms, or amelioration of symptoms of a condition. A therapeutically effective amount may, for example, be sufficient to treat, prevent, reduce the severity, delay the onset, and/or reduce the risk of occurrence of one or more symptoms of a disorder. A therapeutically effective amount, as well as a therapeutically effective frequency of administration, can be determined by methods known in the art and discussed below.

[0206] In some embodiments, the term "therapeutic molecule" refers to a molecule or a compound that is results in prevention, delay of onset of symptoms, or amelioration of symptoms of a condition. In some embodiments, a therapeutic molecule may be, for example, a cytokine, a chemokine, a single chain antibody, a ligand, a metabolic converter, e.g., arginine, a kynurnenine consumer, or an adenosine consumer, a T cell co-stimulatory receptor, a T cell co-stimulatory receptor ligand, an engineered chemotherapy, or a lytic peptide, among others.

[0207] The articles "a" and "an," as used herein, should be understood to mean "at least one," unless clearly indicated to the contrary.

[0208] The phrase "and/or," when used between elements in a list, is intended to mean either (1) that only a single listed element is present, or (2) that more than one element of the list is present. For example, "A, B, and/or C" indicates that the selection may be A alone; B alone; C alone; A and B; A and C; B and C; or A, B, and C. The phrase "and/or" may be used interchangeably with "at least one of" or "one or more of" the elements in a list.

Bacteria

[0209] In one embodiment, the modified microorganism may be a bacterium, e.g., a genetically engineered bacterium. The modified microorganism, or genetically engineered microorganisms, such as the modified bacterium of the disclosure is capable of target-specific delivery of proteins (e.g., viral, bacterial, fungal, and cancer proteins) and/or an immune modulator, such as a STING agonist, to a cell or host. The engineered bacteria may be administered systemically, orally, locally and/or intratumorally. In some embodiments, the genetically engineered bacteria are capable of producing a displayed protein (e.g., viral, bacterial, fungal, and cancer protein), and producing an effector molecule, e.g., an immune modulator, e.g., immune stimulator or sustainer provided herein.

[0210] In certain embodiments, the modified microorganisms or genetically engineered bacteria are obligate anaerobic bacteria. In certain embodiments, the genetically engineered bacteria are facultative anaerobic bacteria. In certain embodiments, the genetically engineered bacteria are aerobic bacteria. In some embodiments, the genetically engineered bacteria are Gram-positive bacteria and lack LPS. In some embodiments, the genetically engineered bacteria are Gram-negative bacteria. In some embodiments, the genetically engineered bacteria are Gram-positive and obligate anaerobic bacteria. In some embodiments, the genetically engineered bacteria are Gram-positive and facultative anaerobic bacteria. In some embodiments, the genetically engineered bacteria are non-pathogenic bacteria. In some embodiments, the genetically engineered bacteria are commensal bacteria. In some embodiments, the genetically engineered bacteria are probiotic bacteria. In some embodiments, the genetically engineered bacteria are naturally pathogenic bacteria that are modified or mutated to reduce or eliminate pathogenicity. Exemplary bacteria include, but are not limited to, Bacillus, Bacteroides, Bifidobacterium, Brevibacteria, Caulobacter, Clostridium, Enterococcus, Escherichia coli, Lactobacillus, Lactococcus, Listeria, Mycobacterium, Saccharomyces, Salmonella, Staphylococcus, Streptococcus, Vibrio, Bacillus coagulans, Bacillus subtilis, Bacteroides fragilis, Bacteroides subtilis, Bacteroides thetaiotaomicron, Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium breve UCC2003, Bifidobacterium infantis, Bifidobacterium lactis, Bifidobacterium longum, Clostridium acetobutylicum, Clostridium butyricum, Clostridium butyricum M-55, Clostridium butyricum miyairi, Clostridium cochlearum, Clostridium felsineum, Clostridium histolyticum, Clostridium multifermentans, Clostridium novyi-NT, Clostridium paraputrificum, Clostridium pasteureanum, Clostridium pectinovorum, Clostridium perfringens, Clostridium roseum, Clostridium sporogenes, Clostridium tertium, Clostridium tetani, Clostridium tyrobutyricum, Corynebacterium parvum, Escherichia coli MG1655, Escherichia coli Nissle 1917, Listeria monocytogenes, Mycobacterium bovis, Salmonella choleraesuis, Salmonella typhimurium, Vibrio cholera. In certain embodiments, the genetically engineered bacteria are selected from the group consisting of Enterococcus faecium, Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus johnsonii, Lactobacillus paracasei, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Lactococcus lactis, and Saccharomyces boulardii. In certain embodiments, the genetically engineered bacteria are selected from the group consisting of Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides subtilis, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium lactis, Clostridium butyricum, Escherichia coli Nissle, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus reuteri, and Lactococcus lactis. In some embodiments, Lactobacillus is used for delivery of one or more immune modulators.

[0211] In some embodiments, the genetically engineered bacteria are obligate anaerobes. In some embodiments, the genetically engineered bacteria are Clostridia and capable of delivery of immune modulators. In some embodiments, the genetically engineered bacteria is selected from the group consisting of Clostridium novyi-NT, Clostridium histolyticium, Clostridium tetani, Clostridium oncolyticum, Clostridium sporogenes, and Clostridium beijerinckii (Liu et al., 2014). In some embodiments, the Clostridium is naturally non-pathogenic. In alternate embodiments, the Clostridium is naturally pathogenic but modified to reduce or eliminate pathogenicity. For example, Clostridium novyi are naturally pathogenic, and Clostridium novyi-NT are modified to remove lethal toxins. Clostridium novyi-NT and Clostridium sporogenes have been used to deliver single-chain HIF-1a antibodies to treat cancer (Groot et al., 2007).

[0212] In some embodiments, the genetically engineered bacteria facultative anaerobes. In some embodiments, the genetically engineered bacteria are Salmonella, e.g., Salmonella typhimurium, and are capable of tumor-specific delivery of immune modulators. Salmonella are non-spore-forming Gram-negative bacteria that are facultative anaerobes. In some embodiments, the Salmonella are naturally pathogenic but modified to reduce or eliminate pathogenicity. For example, Salmonella typhimurium is modified to remove pathogenic sites (attenuated). In some embodiments, the genetically engineered bacteria are Bifidobacterium and capable of immune modulators. Bifidobacterium are Gram-positive, branched anaerobic bacteria. In some embodiments, the Bifidobacterium is naturally non-pathogenic. In alternate embodiments, the Bifidobacterium is naturally pathogenic but modified to reduce or eliminate pathogenicity. Bifidobacterium and Salmonella have been shown to preferentially target and replicate in the hypoxic and necrotic regions of tumors (Yu et al., 2014).

[0213] In some embodiments, the genetically engineered bacteria are Gram-negative bacteria. In some embodiments, the genetically engineered bacteria are E. coli. In some embodiments, the genetically engineered bacteria are Escherichia coli strain Nissle 1917 (E. coli Nissle), a Gram-negative bacterium of the Enterobacteriaceae family that "has evolved into one of the best characterized probiotics" (Ukena et al., 2007). The strain is characterized by its complete harmlessness (Schultz, 2008), and has GRAS (generally recognized as safe) status (Reister et al., 2014, emphasis added).

[0214] The genetically engineered bacteria of the invention may be destroyed, e.g., by defense factors in tissues or blood serum (Sonnenborn et al., 2009). In some embodiments, the genetically engineered bacteria are administered repeatedly. In some embodiments, the genetically engineered bacteria are administered once.

[0215] In certain embodiments, the modified microorganism comprising the display protein is E. coli Nissle strain SYN1557 (delta PAL::CmR).

[0216] In certain embodiments, the effectors and/or immune modulator(s) described herein are expressed in one species, strain, or subtype of genetically engineered bacteria. In alternate embodiments, the effector and/or immune modulator is expressed in two or more species, strains, and/or subtypes of genetically engineered bacteria. One of ordinary skill in the art would appreciate that the genetic modifications disclosed herein may be modified and adapted for other species, strains, and subtypes of bacteria.

[0217] Further examples of bacteria which are suitable are described in International Patent Publication WO/2014/043593, the contents of which is herein incorporated by reference in its entirety. In some embodiments, such bacteria are mutated to attenuate one or more virulence factors.

[0218] In some embodiments, the genetically engineered bacteria of the disclosure proliferate and colonize a host. In some embodiments, colonization persists for several days, several weeks, several months, several years or indefinitely. In some embodiments, the genetically engineered bacteria do not proliferate in the host and bacterial counts drop off quickly post administration, e.g., less than a week post administration, until no longer detectable.

Bacteriophages

[0219] In some embodiments, the genetically engineered bacteria of the disclosure comprise one or more lysogenic, dormant, temperate, intact, defective, cryptic, or satellite phage or bacteriocins/phage tail or gene transfer agents in their natural state. In some embodiments, the prophage or bacteriophage exists in all isolates of a particular bacterium of interest. In some embodiments, the bacteria are genetically engineered derivatives of a parental strain comprising one or more of such bacteriophage. In any of the embodiments described herein, the bacteria may comprise one or more modifications or mutations within a prophage or bacteriophage genome which alters the properties or behavior of the bacteriophage. In some embodiments, the modifications or mutations prevent the prophage from entering or completing the lytic process. In some embodiments, the modifications or mutations prevent the phage from infecting other bacteria of the same or a different type. In some embodiments, the modifications or mutations alter the fitness of the bacterial host. In some embodiments, the modifications or mutations no not alter the fitness of the bacterial host. In some embodiments, the modifications or mutations have an impact on the desired effector function, e.g., on levels of expression of the effector molecule, e.g., immune modulator, e.g., immune stimulator or sustainer, of the genetically engineered bacterium. In some embodiments, the modifications or mutations have no impact on the desired function e.g., on levels of expression of the effector molecule or on levels of activity of the effector molecule.

[0220] Phage genome size varies, ranging from the smallest Leuconostoc phage L5 (2,435 bp), .about.11.5 kbp (e.g. Mycoplasma phage P1), .about.21 kbp (e.g. Lactococcus phage c2), and .about.30 kbp (e.g. Pasteurella phage F108) to the almost 500 kbp genome of Bacillus megaterium phage G (Hatfull and Hendrix; Bacteriophages and their Genomes, Curr Opin Virol. 2011 Oct. 1; 1(4): 298-303, and references therein). Phage genomes may encode less than 10 genes up to several hundreds of genes. Temperate phages or prophages are typically integrated into the chromosome(s) of the bacterial host, although some examples of phages that are integrated into bacterial plasmids also exist (Little, Loysogeny, Prophage Induction, and Lysogenic Conversion. In: Waldor M K, Friedman D I, Adhya S, editors. Phages Their Role in Bacterial Pathogenesis and Biotechnology. Washington D.C.: ASM Press; 2005. pp. 37-54). In some cases, the phages are always located at the same position within the bacterial host chromosome(s), and this position is specific to each phage, i.e., different phages are located at different positions. Other phages can integrate at numerous different locations.

[0221] Accordingly, the bacteria of the disclosure comprise one or more phages genomes which may vary in length, from at least about 1 bp to 10 kb, from at least about 10 kb to 20 kb, from at least about 20 kb to 30 kb, from at least about 30 kb to 40 kb, from at least about 30 kb to 40 kb, from at least about 40 kb to 50 kb, from at least about 50 kb to 60 kb, from at least about 60 kb to 70 kb, from at least about 70 kb to 80 kb, from at least about 80 kb to 90 kb, from at least about 90 kb to 100 kb, from at least about 100 kb to 120 kb, from at least about 120 kb to 140 kb, from at least about 140 kb to 160 kb, from at least about 160 kb to 180 kb, from at least about 180 kb to 200 kb, from at least about 200 kb to 180 kb, from at least about 160 kb to 250 kb, from at least about 250 kb to 300 kb, from at least about 300 kb to 350 kb, from at least about 350 kb to 400 kb, from at least about 400 kb to 500 kb, from at least about 500 kb to 1000 kb. In one embodiment, the genetically engineered bacteria comprise a bacteriophage genome greater than 1000 kb in length.

[0222] In some embodiments, the bacteria of the disclosure comprise one or more phages genomes, which comprise one or more genes encoding one or more polypeptides. In one embodiment, the genetically engineered bacteria comprise a bacteriophage genome comprising at least about 1 to 5 genes, at least about 5 to 10 genes, at least about 10 to 15 genes, at least about 15 to 20 genes, at least about 20 to 25 genes, at least about 25 to 30 genes, at least about 30 to 35 genes, at least about 35 to 40 genes, at least about 40 to 45 genes, at least about 45 to 50 genes, at least about 50 to 55 genes, at least about 55 to 60 genes, at least about 60 to 65 genes, at least about 65 to 70 genes, at least about 70 to 75 genes, at least about 75 to 80 genes, at least about 80 to 85 genes, at least about 85 to 90 genes, at least about 90 to 95 genes, at least about 95 to 100 genes, at least about 100 to 115 genes, at least about 115 to 120 genes, at least about 120 to 125 genes, at least about 125 to 130 genes, at least about 130 to 135 genes, at least about 135 to 140 genes, at least about 140 to 145 genes, at least about 145 to 150 genes, at least about 150 to 160 genes, at least about 160 to 170 genes, at least about 170 to 180 genes, at least about 180 to 190 genes, at least about 190 to 200 genes, at least about 200 to 300 genes. In one embodiment, the genetically engineered bacteria comprise a bacteriophage genome comprising more than about 300 genes.

[0223] In some embodiments, the phage is always or almost always located at the same location or position within the bacterial host chromosome(s) in a particular species. In some embodiments, the phages are found integrated at different locations within the host chromosome in a particular species. In some embodiments, the phage is located on a plasmid.

[0224] In some embodiments, the prophage may be a defective or a cryptic prophage. Defective prophages can no longer undergo a lytic cycle. Cryptic prophages may not be able to undergo a lytic cycle or never have undergone a lytic cycle (Bobay et al., 2014). In some embodiments, the bacteria comprise one or more satellite phage genomes. Satellite phages are otherwise functional phages that do not carry their own structural protein genes, and have genomes that are configures for encapsulation by the structural proteins of other specific phages (Six and Klug Bacteriophage P4: a satellite virus depending on a helper such as prophage P2, Virology, Volume 51, Issue 2, February 1973, Pages 327-344).

[0225] In some embodiments, the bacteria comprise one or more tailiocins. Many bacteria, both gram positive and gram negative, produce a variety of particles resembling phage tails that are functional without an associated phage head (termed tailiocins), and many of which have been shown to have bacteriocin properties (reviewed in Ghequire and Mot, The Tailocin Tale: Peeling off Phage; Trends in Microbiology, October 2015, Vol. 23, No. 10). Phage tail-like bacteriocins are classified two different families: contractile phage tail-like (R-type) and noncontractile but flexible ones (F-type). In some embodiments, the bacteria comprise one or more gene transfer agents. Gene transfer agents (GTAs) are phage-like elements that are encoded by some bacterial genomes. Although GTAs resemble phages, they lack the hallmark capabilities that define typical phages, and they package random fragments of the host cell DNA and then transfer them horizontally to other bacteria of the same species (reviewed in Lang et al., Gene transfer agents: phage-like elements of genetic exchange, Nat Rev Microbiol. 2012 Jun. 11; 10(7): 472-482). There, the DNA can replace the resident cognate chromosomal region by homologous recombination. However, these particles cannot propagate as viruses, as the vast majority of the particles do not carry the genes that encode the GTA. In some embodiments, the bacteria comprise one or more filamentous virions. Filamentous virions integrate as dsDNA prophages (reviewed in Marvin D A, et al, Structure and assembly of filamentous bacteriophages, Prog Biophys Mol Biol. 2014 April; 114(2):80-122). In any of these embodiments, the bacteria described herein comprising defective or a cryptic prophage, satellite phage genomes, tailiocins, gene transfer agents, filamentous virions, which may comprise one or more modifications or mutations within their sequence.

[0226] Prophages can be either identified experimentally or computationally. The experimental approach involves inducing the host bacteria to release phage particles by exposing them to UV light or other DNA-damaging conditions. However, in some cases, the conditions under which a prophage is induced is unknown, and therefore the absence of plaques in a plaque assay does not necessarily prove the absence of a prophage. Additionally, this approach can show only the existence of viable phages, but will not reveal defective prophages. As such, computational identification of prophages from genomic sequence data has become the most preferred route.

[0227] Co-pending International Patent Application PCT/US18/38840, filed Jun. 21, 2018, herein incorporated by reference in their entireties, provide non-limiting examples of probiotic bacteria which contain number of potential bacteriophages contained in the bacterial genome as determined by Phaster scoring. Phaster scoring is described in detail at phaster.ca and in Zhou, et al. ("PHAST: A Fast Phage Search Tool" Nucl. Acids Res. (2011) 39(suppl 2): W347-W352) and Arndt et al. (Arndt, et al. (2016) PHASTER: a better, faster version of the PHAST phage search tool. Nucleic Acids Res., 2016 May 3). In brief, three methods are applied with different criteria to score for prophage regions (as intact, questionable, or incomplete) within a provided bacterial genome sequence.

[0228] In any of the embodiments described herein, the bacteria described herein may comprise one or more modifications or mutations within an existing prophage or bacteriophage genome. In some embodiments, these modifications alter the properties or behavior of the prophage. In some embodiments, the modifications or mutations prevent the prophage from entering or completing the lytic process. In some embodiments, the modifications or mutations prevent the phage from infecting other bacteria of the same or a different type. In some embodiments, the modifications or mutations alter the fitness of the bacterial host. In some embodiments, the modifications or mutations do not alter the fitness of the bacterial host. In some embodiments, the modifications or mutations have an impact on the desired effector function, e.g., of a genetically engineered bacterium. In some embodiments, the modifications or mutations do not have an impact on the desired effector function, e.g., of a genetically engineered bacterium.

[0229] In some embodiments, the modifications or mutations reduce entry or completion of prophage lytic process at least about 1- to 2-fold, at least about 2- to 3-fold, at least about 3- to 4-fold, at least about 4- to 5-fold, at least about 5- to 10-fold, at least about 10 to 100-fold, at least about 100- to 1000-fold. In some embodiments, the modifications or mutations completely prevent entry or completion of prophage lytic process.

[0230] In some embodiments, the modifications or mutations reduce entry or completion of prophage lytic process by at least about 1% to 10%, at least about 10% to 20%, at least about 20% to 30%, at least about 30% to 40%, at least about 40% to 50%, at least about 50% to 60%, at least about 60% to 70%, at least about 70% to 80%, at least about 80% to 90%, or at least about 90% to 100%.

[0231] In some embodiments, the mutations include one or more deletions within the phage genome sequence. In some embodiments, the mutations include one or more insertions into the phage genome sequence. In some embodiments, an antibiotic cassette can be inserted into one or more positions within the phage genome sequence. In some embodiments, the mutations include one or more substitutions within the phage genome sequence. In some embodiments, the mutations include one or more inversions within the phage genome sequence. In some embodiments, the modifications within the phage genome are combinations of two or more of insertions, deletions, substitutions, or inversions within one or more phage genome genes. In any of the embodiments described herein, the modifications may result in one or more frameshift mutations in one or more genes within the phage genome.

[0232] An any of these embodiments, the mutations can be located within or encompass one or more genes encoding proteins of various functions, e.g., lysis, e.g., proteases or lysins, toxins, antibiotic resistance, translation, structural (e.g., head, tail, collar, or coat proteins), bacteriophage assembly, recombination(e.g., integrases, invertases, or transposases), or replication (e.g., primases, tRNA related proteins), phage insertion, attachment, packaging, or terminases.

[0233] In some embodiments, described herein genetically engineered bacteria are engineered Escherichia coli strain Nissle 1917 (E. coli Nissle). As described in co-pending International Patent Application PCT/US18/38840, filed Jun. 21, 2018, herein incorporated by reference in their entireties, in more detail herein in the examples, routine testing procedures identified bacteriophage production from Escherichia coli Nissle 1917 (E. coli Nissle) and related engineered derivatives. To determine the source of the bacteriophage, a collaborative bioinformatics assessment of the genomes of E. coli Nissle, and engineered derivatives was conducted to analyze genomic sequences of the strains for evidence of prophages, to assess any identified prophage elements for the likelihood of producing functional phage, to compare any functional phage elements with other known phage identified among bacterial genomic sequences, and to evaluate the frequency with which prophage elements are found in other sequenced Escherichia coli (E. coli) genomes. The assessment tools included phage prediction software (PHAST and PHASTER), SPAdes genome assembler software, software for mapping low-divergent sequences against a large reference genome (BWA MEM), genome sequence alignment software (MUMmer), and the National Center for Biotechnology Information (NCBI) nonredundant database. The assessment results showed that E. coli Nissle and engineered derivatives analyzed contain three candidate prophage elements, with two of the three (Phage 2 and Phage 3) containing most genetic features characteristic of intact phage genomes. Two other possible phage elements were also identified. Of note, the engineered strains did not contain any additional phage elements that were not identified in parental E. coli Nissle, indicating that plaque-forming units produced by these strains originate from one of these endogenous phages (Phage 3). Interestingly, Phage 3 is unique to E. coli Nissle among a collection of almost 6000 sequenced E. coli genomes, although related sequences limited to short regions of homology with other putative prophage elements are found in a small number of genomes. Phage 3, but not any of the other Phage, was found to be inducible and result in bacterial lysis upon induction.

[0234] Prophages are very common among E. coli strains, with E. coli Nissle containing a relatively small number of prophage sequences compared to the average number found in a well-characterized set of sequenced E. coli genomes. As such, prophage presence in the engineered strains is part of the natural state of this species and the prophage features of the engineered strains analyzed were consistent with the progenitor strain, E. coli Nissle.

[0235] In some embodiments, the bacteria described herein may comprise one or more modifications or mutations within the E. coli Nissle Phage 3 genome which alters the properties or behavior of Phage 3. In some embodiments, the modifications or mutations prevent Phage 3 from entering or completing the lytic process. In some embodiments, the modifications or mutations prevent the E. coli Nissle Phage 3 from infecting other bacteria of the same or a different type. In some embodiments, the modifications or mutations improve the fitness of the bacterial host. In some embodiments, the no effect fitness of the bacterial host is observed. In some embodiments, the modifications or mutations have an impact on the desired effector function, e.g., expression of the immune modulator. In some embodiments, no impact on the desired effector function, e.g., expression of the immune modulator, is observed.

[0236] In some embodiments, the mutations introduced into the bacterial chassis include one or more deletions within the E. coli Nissle Phage 3 genome sequence. In some embodiments, the mutations include one or more insertions into the E. coli Nissle Phage 3 genome sequence. In some embodiments, an antibiotic cassette can be inserted into one or more positions within the E. coli Nissle Phage 3 genome sequence. Mutations within Phage 3 are described in more details in Co-pending U.S. provisional applications 62/523,202 and 62/552,829, herein incorporated by reference in their entireties.

[0237] In one specific embodiment, at least about 9000 to 10000 bp of the E. coli Nissle Phage 3 genome are mutated, e.g., in one example, 9687 bp of the E. coli Nissle Phage 3 genome are deleted.

[0238] In any of the embodiments described herein, the modifications encompass are located in one or more genes selected from ECOLIN_09965, ECOLIN_09970, ECOLIN_09975, ECOLIN_09980, ECOLIN_09985, ECOLIN_09990, ECOLIN_09995, ECOLIN_10000, ECOLIN_10005, ECOLIN_10010, ECOLIN_10015, ECOLIN_10020, ECOLIN_10025, ECOLIN_10030, ECOLIN_10035, ECOLIN_10040, ECOLIN_10045, ECOLIN_10050, ECOLIN_10055, ECOLIN_10065, ECOLIN_10070, ECOLIN_10075, ECOLIN_10080, ECOLIN_10085, ECOLIN_10090, ECOLIN_10095, ECOLIN_10100, ECOLIN_10105, ECOLIN_10110, ECOLIN_10115, ECOLIN_10120, ECOLIN_10125, ECOLIN_10130, ECOLIN_10135, ECOLIN_10140, ECOLIN_10145, ECOLIN_10150, ECOLIN_10160, ECOLIN_10165, ECOLIN_10170, ECOLIN_10175, ECOLIN_10180, ECOLIN_10185, ECOLIN_10190, ECOLIN_10195, ECOLIN_10200, ECOLIN_10205, ECOLIN_10210, ECOLIN_10220, ECOLIN_10225, ECOLIN_10230, ECOLIN_10235, ECOLIN_10240, ECOLIN_10245, ECOLIN_10250, ECOLIN_10255, ECOLIN_10260, ECOLIN_10265, ECOLIN_10270, ECOLIN_10275, ECOLIN_10280, ECOLIN_10290, ECOLIN_10295, ECOLIN_10300, ECOLIN_10305, ECOLIN_10310, ECOLIN_10315, ECOLIN_10320, ECOLIN_10325, ECOLIN_10330, ECOLIN_10335, ECOLIN_10340, and ECOLIN_10345.

[0239] In one embodiment, the mutation is a complete or partial deletion of one or more of ECOLIN_10110, ECOLIN_10115, ECOLIN_10120, ECOLIN_10125, ECOLIN_10130, ECOLIN_10135, ECOLIN_10140, ECOLIN_10145, ECOLIN_10150, ECOLIN_10160, ECOLIN_10165, ECOLIN_10170, and ECOLIN_10175. In one specific embodiment, the mutation is a complete or partial deletion of ECOLIN_10110, ECOLIN_10115, ECOLIN_10120, ECOLIN_10125, ECOLIN_10130, ECOLIN_10135, ECOLIN_10140, ECOLIN_10145, ECOLIN_10150, ECOLIN_10160, ECOLIN_10165, and ECOLIN_10170, and ECOLIN_10175. In one specific embodiment, the mutation is a complete deletion of ECOLIN_10110, ECOLIN_10115, ECOLIN_10120, ECOLIN_10125, ECOLIN_10130, ECOLIN_10135, ECOLIN_10140, ECOLIN_10145, ECOLIN_10150, ECOLIN_10160, ECOLIN_10165, and ECOLIN_10170, and a deletion mutation of ECOLIN_10175.

Effector Molecules

Oncolysis and Activation of an Innate Immune Response

[0240] In certain embodiments, the effector molecule(s), or immune modulators(s) of the disclosure generates an innate immune response. In certain embodiments, the immune modulators(s) of the disclosure generates a local immune response. In some aspects, the effector molecule, or immune modulator, is able to activate systemic immunity against displayed proteins (e.g., viral, bacterial, fungal, and cancer proteins). In certain embodiments, the immune modulators(s) generates a systemic or adaptive immune response. In some embodiments, the immune modulators(s) result in long-term immunological memory. Examples of suitable immune modulators(s), e.g., immune initiators and/or immune sustainers are described herein.

[0241] In some embodiments, one or more immune modulators may be produced by a modified microorganism described herein. In other embodiments, one or more immune modulators may be administered in combination with a modified microorganism capable of producing a second immune modulator(s). For example, one or more immune initiators may be administered in combination with a modified microorganism capable of producing one or more immune sustainers. In another embodiment, one or more immune sustainers may be administered in combination with a modified microorganism capable of producing one or more immune initiators. Alternatively, one or more first immune initiators may be administered in combination with a modified microorganism capable of producing one or more second immune initiators. Alternatively, one or more first immune sustainers may be administered in combination with a modified microorganism capable of producing one or more second immune sustainers.

Displayed Proteins/Vaccines

[0242] By introducing a displayed protein, e.g., viral, bacterial, fungal, or cancer protein, to the local environment, an immune response can be raised against the particular microbe, cancer, or infected cell of interest known to be associated with that protein.

[0243] By introducing viral proteins, e.g., a spike viral protein, to the local environment, an immune response can be raised against the particular virus or infected cell of interest known to be associated with that protein. As used herein the term "viral protein" is meant to refer to virus-specific proteins, and/or virus-associated proteins, e.g., a spike protein of SARV-CoV-2, e.g., the receptor binding domain (RBD) of a spike protein of SARV-CoV-2. The engineered microorganisms can be engineered such that the peptides, e.g. viral proteins, e.g., the receptor binding domain (RBD) of a spike protein of SARV-CoV-2, can be anchored in the microbial cell wall (e.g., at the microbial cell surface). Thus, in some embodiments, the genetically engineered bacteria, are engineered to produce one or more viral proteins. Non-limiting examples of such viral proteins which may be produced by the bacteria of the disclosure described e.g., in Liu W J., et al. 2017, Antiviral Research 137:82-92; Huang J., et al. 2007, Vaccine 25: 6981-6991; Chen H., et al., 2005, J Immunol 175: 591-598; Ahmed S. F., et al., 2020, Viruses 12: 254; and Grifoni A., et al., Cell Host & Microbe 27: 1-10; the contents of each of which is herein incorporated by reference in its entirety or otherwise known in the art.

[0244] In any of these embodiments, the genetically engineered bacteria comprising gene sequence(s) encoding displayed proteins further comprise gene sequence(s) encoding one or more further effector molecule(s), i.e., therapeutic molecule(s) or a metabolic converter(s). In any of these embodiments, the circuit encoding antigens may be combined with a circuit encoding one or more immune initiators or immune sustainers as described herein, in the same or a different bacterial strain (combination circuit or mixture of strains). The circuit encoding the immune initiators or immune sustainers may be under the control of a constitutive or inducible promoter, e.g., low oxygen inducible promoter or any other constitutive or inducible promoter described herein. In any of these embodiments, the gene sequence(s) encoding proteins may be combined with gene sequence(s) encoding one or more STING agonist producing enzymes, as described herein, in the same or a different bacterial strain (combination circuit or mixture of strains). In some embodiments, the gene sequences which are combined with the gene sequence(s) encoding proteins encode DacA. DacA may be under the control of a constitutive or inducible promoter, e.g., low oxygen inducible promoter such as FNR or any other constitutive or inducible promoter described herein. In some embodiments, the dacA gene is integrated into the chromosome. In some embodiments, the gene sequences which are combined with the gene sequence(s) encoding proteins encode cGAS. cGAS may be under the control of a constitutive or inducible promoter, e.g., low oxygen inducible promoter such as FNR or any other constitutive or inducible promoter described herein. In some embodiments, the gene encoding cGAS is integrated into the chromosome. In any of these combination embodiments, the bacteria may further comprise an auxotrophic modification, e.g., a mutation or deletion in DapA, ThyA, or both. In any of these embodiments, the bacteria may further comprise a phage modification, e.g., a mutation or deletion, in an endogenous prophage as described herein.

STING A Agonists

[0245] Stimulator of interferon genes (STING) protein was shown to be a critical mediator of the signaling triggered by cytosolic nucleic acid derived from DNA viruses, bacteria, and tumor-derived DNA. The ability of STING to induce type I interferon production lead to studies in the context of antitumor immune response, and as a result, STING has emerged to be a potentially potent target in many different immunotherapies. A large part of the effects caused by STING activation may depend upon production of IFN-.beta. by APCs and improved antigen presentation by these cells, which promotes CD8+ T cell priming against viral proteins. However, STING protein is also expressed broadly in a variety of cell types including myeloid-derived suppressor cells (MDSCs) and cancer cells, in which the function of the pathway has not yet been well characterized (Sokolowska, O. & Nowis, D; STING Signaling in Cancer Cells: Important or Not?; Archivum Immunologiae et Therapiae Experimentalis; Arch. Immunol. Ther. Exp. (2018) 66: 125).

[0246] Stimulator of interferon genes (STING), also known as transmembrane protein 173 (TMEM173), mediator of interferon regulatory factor 3 activation (MITA), MPYS or endoplasmic reticulum interferon stimulator (ERIS), is a dimeric protein which is mainly expressed in macrophages, T cells, dendritic cells, endothelial cells, and certain fibroblasts and epithelial cells. STING plays an important role in the innate immune response--mice lacking STING are viable though prone to lethal infection following exposure to a variety of microbes. STING functions as a cytosolic receptor for the second messengers in the form of cytosolic cyclic dinucleotides (CDNs), such as cGAMP and the bacterial second messengers c-di-GMP and c-di-AMP. Upon stimulation by the CDN a conformational change in STING occurs. STING translocates from the ER to the Golgi apparatus and its carboxyterminus is liberated, This leads to the activation of TBK1 (TANK-binding kinase 1)/IRF3 (interferon regulatory factor 3), NF-.kappa.B, and STAT6 signal transduction pathways, and thereby promoting type I interferon and proinflammatory cytokine responses. CDNs include canonical cyclic di-GMP (c[G(30-50)pG(30-50)p] or cyclic di-AMP or cyclic GAMP (cGMP-AMP) (Barber, STING-dependent cytosolic DNA sensing pathways; Trends Immunol. 2014 February; 35(2):88-93).

[0247] CDNs can be exogenously (i.e., bacterially) and/or endogenously produced (i.e., within the host by a host enzyme upon exposure to dsDNA). STING is able to recognize various bacterial second messenger molecules cyclic diguanylate monophosphate (c-di-GMP) and cyclic diadenylate monophosphate (c-di-AMP), which triggers innate immune signaling response (Ma et al. The cGAS-STING Defense Pathway and Its Counteraction by Viruses; Cell Host & Microbe 19, Feb. 10, 2016). Additionally cyclic GMPAMP (cGAMP) can also bind to STING and result inactivation of IRF3 and .beta.-interferon production. Both 3'5'-3'5' cGAMP (3'3' cGAMP) produced by Vibrio cholerae, and the metazoan secondary messenger cyclic [G(2',5')pA(3'5')] (2'3' cGAMP), could activate the innate immune response through STING pathway (Yi et al., Single Nucleotide Polymorphisms of Human STING Can Affect Innate Immune Response to Cyclic Dinucleotides; PLOS One (2013). 8(10)e77846, an references therein). Bacterial and metazoan (e.g., human) c-di-GAMP synthases (cGAS) utilizes GTP and ATP to generate cGAMP capable of STING activation. In contrast to prokaryotic CDNs, which have two canonical 30-50 phosphodiester linkages, the human cGAS product contains a unique 20-50 bond resulting in a mixed linkage cyclic GMP-AMP molecule, denoted as 2',3' cGAMP (as described in (Kranzusch et al., Ancient Origin of cGAS-STING Reveals Mechanism of Universal 2',3' cGAMP Signaling; Molecular Cell 59, 891-903, Sep. 17, 2015 and references therein). The bacterium Vibrio cholerae encodes an enzyme called DncV that is a structural homolog of cGAS and synthesizes a related second messenger with canonical 3'-5' bonds (3',3' cGAMP).

[0248] Components of the stimulator of interferon genes (STING) pathway plays an important role in the detection of tumor cells by the immune system. In preclinical studies, cyclic dinucleotides (CDN), naturally occurring or rationally designed synthetic derivatives, are able to promote an aggressive antitumor response. For example, when co-formulated with an irradiated GM-CSF-secreting whole-cell vaccine in the form of STINGVAX, synthetic CDNs increased the antitumor efficacy and STINGVAX combined with PD-1 blockade induced regression of established tumors (Fu et al., STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade; Sci Transl Med. 2015 Apr. 15; 7(283): 283ra52). In another example, Smith et al. conducted a study showing that STING agonists may augment CAR T therapy by stimulating the immune response to eliminate tumor cells that are not recognized by the adoptively transferred lymphocytes and thereby improve the effectiveness of CAR T cell therapy (Smith et al., Biopolymers co-delivering engineered T cells and STING agonists can eliminate heterogeneous tumors; J Clin Invest. 2017 Jun. 1; 127(6):2176-2191).

[0249] In some embodiments, the genetically engineered bacterium is capable of producing one or more STING agonists. Non limiting examples of STING agonists which can be produced by the genetically engineered bacteria of the disclosure include 3'3' cGAMP, 2'3'cGAMP, 2'2'-cGAMP, 2'2'-cGAMP VacciGrade.TM. (Cyclic [G(2',5')pA(2',5')p]), 2'3'-cGAMP, 2'3'-cGAMP VacciGrade.TM. (Cyclic [G(2',5')pA(3',5')p]), 2'3'-cGAM(PS)2 (Rp/Sp), 3'3'-cGAMP, 3'3'-cGAMP VacciGrade.TM. (Cyclic [G(3',5')pA(3',5')p]), c-di-AMP, c-di-AMP VacciGrade.TM. (Cyclic diadenylate monophosphate Th1/Th2 response), 2'3'-c-di-AMP, 2'3'-c-di-AM(PS)2 (Rp,Rp) (Bisphosphorothioate analog of c-di-AMP, Rp isomers), 2'3'-c-di-AM(PS)2 (Rp,Rp) VacciGrade.TM. c-di-GMP, c-di-GMP VacciGrade.TM., 2'3'-c-di-GMP, and c-di-IMP. In some embodiments, the genetically engineered bacterium is that comprises a gene encoding one or more enzymes for the production of one or more STING agonists. Cyclic-di-GAMP synthase (cdi-GAMP synthase or cGAS) produces the cyclic-di-GAMP from one ATP and one GTP. In some embodiments, the enzymes are c-di-GAMP synthases (cGAS). In one embodiment, the genetically engineered bacteria comprise one or more gene sequences for the expression of an enzyme in class EC 2.7.7.86. In some embodiments, such enzymes are bacterial enzymes. In some embodiments, the enzyme is a bacterial c-di-GMP synthase. In some embodiments, the enzyme is a bacterial c-GAMP synthase (GMP-AMP synthase). In some embodiments, the bacteria are capable of producing 3'3' c-dGAMP.

[0250] In some embodiments, the bacteria are capable of producing 3'3'-cGAMP. According to the instant disclosure several enzymes suitable for production of 3'3'-cGAM P from genetically engineered bacteria were identified. These enzymes include the Vibrio cholerae cGAS orthologs from Verminephrobacter eiseniae (EF01-2 Earthworm symbiont), Kingella denitrificans (ATCC 33394), and Neisseria bacilliformis (ATCC BAA-1200). Accordingly, in some embodiments, the genetically engineered bacteria comprise gene sequences encoding cGAS from Vibrio cholerae. Accordingly, in some embodiments, the genetically engineered bacteria comprise gene sequences encoding one or more Vibrio cholerae cGAS orthologs from species selected from Verminephrobacter eiseniae (EF01-2 Earthworm symbiont), Kingella denitrificans (ATCC 33394), and Neisseria bacilliformis (ATCC BAA-1200). In some embodiments, the bacteria comprise a gene sequence encoding DncV. In some embodiments, DncV is from Vibrio cholerae. In one embodiment, the DncV orthologue is from Verminephrobacter eiseniae. In one embodiment, the DncV orthrolog is from Kingella denitrificans. In one embodiment, the DncV orthrolog is from Neisseria bacilliformis. In some embodiments, the genetically engineered bacteria comprise a gene sequence encoding a DncV orthologue from a species selected from Enhydrobacter aerosaccus, Kingella denitrificans, Neisseria bacilliformis, Phaeobacter gallaeciensi, Citromicrobium sp., Roseobacter litoralis, Roseovarius sp., Methylobacterium populi, Erythrobacter sp., Erythrobacter litoralis, Methylophaga thiooxydans, Methylophaga thiooxydans, Herminiimonas arsenicoxydans, Verminephrobacter eiseniae, Methylobacter tundripaludum, Psychrobacter arcticus, Vibrio cholerae, Vibrio sp, Aeromonas salmonicida, Serratia odorifera, Verminephrobacter eiseniae, and Methylovorus glucosetrophus.

[0251] In some embodiments, the genetically engineered bacteria are capable of producing 2'3'-cGAMP. Human cGAS is known to produce 2'3'-cGAMP. In some embodiments, the genetically engineered bacteria comprise gene sequences encoding human cGAS.

[0252] In some embodiments, the genetically engineered bacteria are capable of increasing c-GAMP (2'3' or 3'3') levels in the microenvironment. In some embodiments, the genetically engineered bacteria are capable of increasing c-GAMP levels in the intracellular space In some embodiments, the genetically engineered bacteria are capable of increasing c-GAMP levels inside of a eukaryotic cell. In some embodiments, the genetically engineered bacteria are capable of increasing c-GAMP (2'3' or 3'3') levels inside of an immune cell. In some embodiments, the cell is a phagocyte. In some embodiments, the cell is a macrophage. In some embodiments, the cell is a dendritic cell. In some embodiments, the cell is a neutrophil. In some embodiments, the cell is a MDSC. In some embodiments, the genetically engineered bacteria are capable of increasing c-GAMP (2'3' or 3'3') inside of a cell. In some embodiments, the genetically engineered bacteria are capable of increasing c-GAMP levels in vitro in the bacterial cell and/or in the growth medium.

[0253] In one embodiment, the genetically engineered bacteria comprise gene sequence(s) encoding bacterial c-di-GAMP synthase from Vibrio cholerae. In some embodiments, the enzyme is DncV.

[0254] In one embodiment, the genetically engineered bacteria comprise gene sequence(s) encoding c-di-AMP synthase from Verminephrobacter eiseniae. In one embodiment, the bacterial c-di-GAMP synthase is DcnV orthologue from Verminephrobacter eiseniae (EF01-2 Earthworm symbiont). In some embodiments, the genetically engineered bacteria comprise c-di-GAMP synthase gene sequence(s) encoding one or more polypeptide(s) comprising SEQ ID NO: 1262 or functional fragments thereof. In some embodiments, genetically engineered bacteria comprise a gene sequence encoding a polypeptide that has at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% identity to SEQ ID NO: 1262 or a functional fragment thereof. In some embodiments, the polypeptide has at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 1262. In some specific embodiments, the polypeptide comprises SEQ ID NO: 1262. In other specific embodiments, the polypeptide consists of SEQ ID NO: 1262. In certain embodiments, the bacterial c-di-GAMP synthase gene sequence has at least about 80% identity with SEQ ID NO: 1265. In certain embodiments, the gene sequence has at least about 90% identity with SEQ ID NO: 1265. In certain embodiments, the gene sequence has at least about 95% identity with SEQ ID NO: 1265. In some embodiments, the gene sequence has at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 1265. In some specific embodiments, the gene sequence comprises SEQ ID NO: 1265. In other specific embodiments, the gene sequence consists of SEQ ID NO: 1265.

[0255] In one embodiment, the genetically engineered bacteria comprise gene sequence(s) encoding c-di-AMP synthase from Kingella denitrificans (ATCC 33394). In one embodiment, the bacterial c-di-GAMP synthase is DcnV orthologue from Kingella denitrificans. In some embodiments, the genetically engineered bacteria comprise c-di-GAMP synthase gene sequence(s) encoding one or more polypeptide(s) comprising SEQ ID NO: 1260 or functional fragments thereof. In some embodiments, genetically engineered bacteria comprise a gene sequence encoding a polypeptide that has at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% identity to SEQ ID NO: 1260 or a functional fragment thereof. In some embodiments, the polypeptide has at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 1260. In some specific embodiments, the polypeptide comprises SEQ ID NO: 1260. In other specific embodiments, the polypeptide consists of SEQ ID NO: 1260. In certain embodiments, the bacterial c-di-GAMP synthase gene sequence has at least about 80% identity with SEQ ID NO: 1263. In certain embodiments, the gene sequence has at least about 90% identity with SEQ ID NO: 1263. In certain embodiments, the gene sequence has at least about 95% identity with SEQ ID NO: 1263. In some embodiments, the gene sequence has at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 1263. In some specific embodiments, the gene sequence comprises SEQ ID NO: 1263. In other specific embodiments, the gene sequence consists of SEQ ID NO: 1263.

[0256] In one embodiment, the genetically engineered bacteria comprise gene sequence(s) encoding c-di-AMP synthase from Neisseria bacilliformis (ATCC BAA-1200). In one embodiment, the bacterial c-di-GAMP synthase is DcnV orthologue from Neisseria bacilliformis. In some embodiments, the genetically engineered bacteria comprise c-di-GAMP synthase gene sequence(s) encoding one or more polypeptide(s) comprising SEQ ID NO: 1261 or functional fragments thereof. In some embodiments, genetically engineered bacteria comprise a gene sequence encoding a polypeptide that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% identity to SEQ ID NO: 1261 or a functional fragment thereof. In some embodiments, the polypeptide has at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 1261. In some specific embodiments, the polypeptide comprises SEQ ID NO: 1261. In other specific embodiments, the polypeptide consists of SEQ ID NO: 1261. In certain embodiments, the c-di-GAMP synthase sequence has at least about 80% identity with SEQ ID NO: 1264. In certain embodiments, the gene sequence has at least about 90% identity with SEQ ID NO: 1264. In certain embodiments, the gene sequence has at least about 95% identity with SEQ ID NO: 1264. In some embodiments, the gene sequence has at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 1264. In some specific embodiments, the gene sequence comprises SEQ ID NO: 1264. In other specific embodiments, the gene sequence consists of SEQ ID NO: 1264.

[0257] In one embodiment, the genetically engineered bacteria comprise gene sequence(s) encoding mammalian c-di-GAMP enzymes. In some embodiments, the STING agonist producing enzymes are human enzymes. In some embodiments, the gene sequence(s) are codon-optimized for expression in a microorganism host cell. In one embodiment, the genetically engineered bacteria comprise gene sequence(s) encoding the human polypeptide cGAS. In some embodiments, the genetically engineered bacteria comprise human cGAS gene sequence(s) encoding one or more polypeptide(s) comprising SEQ ID NO: 1254 or functional fragments thereof. In some embodiments, genetically engineered bacteria comprise a gene sequence encoding a polypeptide that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% identity to SEQ ID NO: 1254 or a functional fragment thereof. In some embodiments, the polypeptide has at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 1254. In some specific embodiments, the polypeptide comprises SEQ ID NO: 1254. In other specific embodiments, the polypeptide consists of SEQ ID NO: 1254. In certain embodiments, the human cGAS sequence has at least about 80% identity with SEQ ID NO: 1255. In certain embodiments, the gene sequence has at least about 90% identity with SEQ ID NO: 1255. In certain embodiments, the gene sequence has at least about 95% identity with SEQ ID NO: 1255. In some embodiments, the gene sequence has at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 1255. In some specific embodiments, the gene sequence comprises SEQ ID NO: 1264. In other specific embodiments, the gene sequence consists of SEQ ID NO: 1255.

[0258] In some embodiments, the bacteria are capable of producing cyclic-di-GMP. Accordingly, in some embodiments, the genetically engineered bacteria comprise gene sequence(s) encoding one or more diguanylate cyclase(s).

[0259] In some embodiments, the genetically engineered bacteria are capable of increasing cyclic-di-GMP levels in the microenvironment. In some embodiments, the genetically engineered bacteria are capable of increasing cyclic-di-GMP levels in the intracellular space In some embodiments, the genetically engineered bacteria are capable of increasing cyclic-di-GMP levels inside of a eukaryotic cell. In some embodiments, the genetically engineered bacteria are capable of increasing cyclic-di-GMP levels inside of an immune cell. In some embodiments, the cell is a phagocyte. In some embodiments, the cell is a macrophage. In some embodiments, the cell is a dendritic cell. In some embodiments, the cell is a neutrophil. In some embodiments, the cell is a MDSC. In some embodiments, the genetically engineered bacteria are capable of increasing c cyclic-di-GMP levels inside of a cell. In some embodiments, the genetically engineered bacteria are capable of increasing c-GMP levels in vitro in the bacterial cell and/or in the growth medium.

[0260] In some embodiments, the genetically engineered bacteria are capable of producing c-diAMP. Diadenylate cyclase produces one molecule cyclic-di-AMP from two ATP molecules. In one embodiment, the genetically engineered bacteria comprise one or more gene sequences for the expression of a diadenylate cyclase. In one embodiment, the genetically engineered bacteria comprise one or more gene sequences for the expression of an enzyme in class EC 2.7.7.85. In one embodiment, the diadenylate cyclase is a bacterial diadenylate cyclase. In one embodiment, the diadenylate cyclase is DacA. In one embodiment, the DacA is from Listeria monocytogenes.

[0261] In some embodiments, the genetically engineered bacteria comprise DacA gene sequence(s) encoding one or more polypeptide(s) comprising SEQ ID NO: 1257 or functional fragments thereof. In some embodiments, genetically engineered bacteria comprise a gene sequence encoding a polypeptide that has at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% identity to SEQ ID NO: 1257 or a functional fragment thereof. In some embodiments, the polypeptide has at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 1257. In some specific embodiments, the polypeptide comprises SEQ ID NO: 1257. In other specific embodiments, the polypeptide consists of SEQ ID NO: 1257. In certain embodiments, the Dac A sequence has at least about 80% identity with SEQ ID NO: 1258. In certain embodiments, the gene sequence has at least about 90% identity with SEQ ID NO: 1258. In certain embodiments, the gene sequence has at least about 95% identity with SEQ ID NO: 1258. In some embodiments, the gene sequence has at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 1258. In some specific embodiments, the gene sequence comprises SEQ ID NO: 1258. In other specific embodiments, the gene sequence consists of SEQ ID NO: 1258.

[0262] In some embodiments, the genetically engineered bacteria comprise DacA gene sequence(s) operably linked to a promoter which is inducible under low oxygen conditions, e.g., an FNR inducible promoter as described herein. In certain embodiments, the sequence of the DacA gene operably linked to the FNR inducible promoter has at least about 80% identity with SEQ ID NO: 1284. In certain embodiments, the sequence of the DacA gene operably linked to the FNR inducible promoter has at least about 90% identity with SEQ ID NO: 1258. In certain embodiments, the sequence of the DacA gene operably linked to the FNR inducible promoter has at least about 95% identity with SEQ ID NO: 1258. In some embodiments, the sequence of the DacA gene operably linked to the FNR inducible promoter has at least about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 1258. In some specific embodiments, the sequence of the DacA gene operably linked to the FNR inducible promoter comprises SEQ ID NO: 1258. In other specific embodiments the sequence of the DacA gene operably linked to the FNR inducible promoter consists of SEQ ID NO: 1258.

[0263] Other suitable diadenylate cyclases are known in the art and include those include in the EggNog database (http://eggnogdb.embl.de). Non-limiting examples of diadenylate cyclases which can be expressed by the bacteria include Megasphaera sp. UPII 135-E (HMPREF1040_0026), Streptococcus anginosus SK52=DSM 20563 (HMPREF9966_0555), Streptococcus mitis bv. 2 str. SK95 (HMPREF9965_1675), Streptococcus infantis SK1076 (HMPREF9967_1568), Acetonema longum DSM 6540 (ALO_03356), Sporosarcina newyorkensis 2681 (HMPREF9372_2277), Listeria monocytogenes str. Scott A (BN418_2551), Candidatus arthromitus sp. SFB-mouse-Japan (SFBM_1354), Haloplasma contractile SSD-17B 2 seqs HLPCO_01750, HLPCO_08849), Lactobacillus kefiranofaciens ZW3 (WANG_0941), Mycoplasma anatis 1340 (GIG_03148), Streptococcus constellatus subsp. pharyngis SK1060=CCUG 46377 (HMPREF1042_1168), Streptococcus infantis SK970 (HMPREF9954_1628), Paenibacillus mucilaginosus KNP414 (YBBP), Nostoc sp. PCC 7120 (ALL2996), Mycoplasma columbinum SF7 (MCSF7_01321), Lactobacillus ruminis SPM0211 (LRU_01199), Candidatus arthromitus sp. SFB-rat-Yit (RATSFB_1182), Clostridium sp. SY8519 (CXIVA_02190), Brevibacillus laterosporus LMG 15441 (BRLA_C02240), Weissella koreensis KACC 15510 (WKK_01955), Brachyspira intermedia PWS/A (BINT_2204), Bizionia argentinensis JUB59 (BZARG_2617), Streptococcus salivarius 57.1 (SSAL_01348), Alicyclobacillus acidocaldarius subsp. acidocaldarius Tc-4-1 (TC41_3001), Sulfobacillus acidophilus TPY (TPY_0875), Streptococcus pseudopneumoniae IS7493 (SPPN_07660), Megasphaera elsdenii DSM 20460 (MELS_0883), Streptococcus infantarius subsp. infantarius CJ18 (SINF_1263), Blattabacterium sp. (Mastotermes darwiniensis) str. MADAR (MADAR_511), Blattabacterium sp. (Cryptocercus punctulatus) str. Cpu (BLBCPU_093), Synechococcus sp. CC9605 (SYNCC9605_1630), Thermus sp. CCB_US3_UFI (AEV17224.1), Mycoplasma haemocanis str. Illinois (MHC_04355), Streptococcus macedonicus ACA-DC 198 (YBBP), Mycoplasma hyorhinis GDL-1 (MYM_0457), Synechococcus elongatus PCC 7942 (SYNPCC7942_0263), Synechocystis sp. PCC 6803 (SLL0505), Chlamydophila pneumoniae CWL029 (YBBP), Microcoleus chthonoplastes PCC 7420 (MC7420_6818), Persephonella marina EX-H1 (PERMA_1676), Desulfitobacterium hafniense Y51 (DSY4489), Prochlorococcus marinus str. AS9601 (A9601_11971), Flavobacteria bacterium BBFL7 (BBFL7_02553), Sphaerochaeta globus str. Buddy (SPIBUDDY_2293), Sphaerochaeta pleomorpha str. Grapes (SPIGRAPES_2501), Staphylococcus aureus subsp. aureus Mu50 (SAV2163), Streptococcus pyogenes M1 GAS (SPY_1036), Synechococcus sp. WH 8109 (SH8109_2193), Prochlorococcus marinus subsp. marinus str. CCMP1375 (PRO_1104), Prochlorococcus marinus str. MIT 9515 (P9515_11821), Prochlorococcus marinus str. MIT 9301 (P9301_11981), Prochlorococcus marinus str. NATL1A (NATL1_14891), Listeria monocytogenes EGD-e (LMO2120), Streptococcus pneumoniae TIGR4 2 seqs SPNET_02000368, SP_1561), Streptococcus pneumoniae R6 (SPR1419), Staphylococcus epidermidis RP62A (SERP1764), Staphylococcus epidermidis ATCC 12228 (SE_1754), Desulfobacterium autotrophicum HRM2 (HRM2_32880), Desulfotalea psychrophila LSv54 (DP1639), Cyanobium sp. PCC 7001 (CPCC7001_1029), Chlamydophila pneumoniae TW-183 (YBBP), Leptospira interrogans serovar Lai str. 56601 (LA_3304), Clostridium perfringens ATCC 13124 (CPF_2660), Thermosynechococcus elongatus BP-1 (TLR1762), Bacillus anthracis str. Ames (BA_0155), Clostridium thermocellum ATCC 27405 (CTHE_1166), Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293 (LEUM_1568), Oenococcus oeni PSU-1 (OEOE_1656), Trichodesmium erythraeum IMS101 (TERY_2433), Tannerella forsythia ATCC 43037 (BFO_1347), Sulfurihydrogenibium azorense Az-Fu1 (SULAZ_1626), Candidatus koribacter versatilis Ellin345 (ACID345_0278), Desulfovibrio alaskensis G20 (DDE_1515), Carnobacterium sp. 17-4 (YBBP), Streptococcus mutans UA159 (SMU_1428C), Mycoplasma agalactiae (MAG3060), Streptococcus agalactiae NEM316 (GBS0902), Clostridium tetani E88 (CTC_02549), Ruminococcus champanellensis 18P13 (RUM_14470), Croceibacter atlanticus HTCC2559 (CA2559_13513), Streptococcus uberis 0140J (SUB1092), Chlamydophila abortus S26/3 (CAB642), Lactobacillus plantarum WCFS1 (LP_0818), Oceanobacillus iheyensis HTE831 (OB0230), Synechococcus sp. RS9916 (RS9916_31367), Synechococcus sp. RS9917 (RS9917_00967), Bacillus subtilis subsp. subtilis str. 168 (YBBP), Aquifex aeolicus VF5 (AQ_1467), Borrelia burgdorferi B31 (BB_0008), Enterococcus faecalis V583 (EF_2157), Bacteroides thetaiotaomicron VPI-5482 (BT_3647), Bacillus cereus ATCC 14579 (BC_0186), Chlamydophila caviae GPIC (CCA_00671), Synechococcus sp. CB0101 (SCB01_010100000902), Synechococcus sp. CB0205 (SCB02_010100012692), Candidatus Solibacter usitatus Ellin6076 (ACID_1909), Geobacillus kaustophilus HTA426 (GK0152), Verrucomicrobium spinosum DSM 4136 (VSPID_010100022530), Anabaena variabilis ATCC 29413 (AVA_0913), Porphyromonas gingivalis W83 (PG_1588), Chlamydia muridarum Nigg (TC_0280), Deinococcus radiodurans R1 (DR_0007), Geobacter sulfurreducens PCA 2 seqs GSU1807, GSU0868), Mycoplasma arthritidis 158L3-1 (MARTH_ORF527), Mycoplasma genitalium G37 (MG105), Treponema denticola ATCC 35405 (TDE_1909), Treponema pallidum subsp. pallidum str. Nichols (TP_0826), butyrate-producing bacterium SS3/4 (CK3_23050), Carboxydothermus hydrogenoformans Z-2901 (CHY_2015), Ruminococcus albus 8 (CUS_5386), Streptococcus mitis NCTC 12261 (SM12261_1151), Gloeobacter violaceus PCC 7421 (GLL0109), Lactobacillus johnsonii NCC 533 (U_0892), Exiguobacterium sibiricum 255-15 (EXIG_0138), Mycoplasma hyopneumoniae J (MHJ_0485), Mycoplasma synoviae 53 (MS53_0498), Thermus thermophilus HB27 (TT_C1660), Onion yellows phytoplasma OY-M (PAM_584), Streptococcus thermophilus LMG 18311 (OSSG), Candidatus Protochlamydia amoebophila UWE25 (PC1633), Chlamydophila felis Fe/C-56 (CF0340), Bdellovibrio bacteriovorus HD100 (BD1929), Prevotella ruminicola 23 (PRU_2261), Moorella thermoacetica ATCC 39073 (MOTH_2248), Leptospira interrogans serovar Copenhageni str. Fiocruz L1-130 (LIC_10844), Mycoplasma mobile 163K (MMOB4550), Synechococcus elongatus PCC 6301 (SYC1250_C), Cytophaga hutchinsonii ATCC 33406 (CHU_3222), Geobacter metallireducens GS-15 2 seqs GMET_1888, GMET_1168), Bacillus halodurans C-125 (BH0265), Bacteroides fragilis NCTC 9343 (BF0397), Chlamydia trachomatis D/UW-3/CX (YBBP), Clostridium acetobutylicum ATCC 824 (CA_C3079), Clostridium difficile 630 (CD0110), Lactobacillus acidophilus NCFM (LBA0714), Lactococcus lactis subsp. lactis 111403 (YEDA), Listeria innocua Clip11262 (LIN2225), Mycoplasma penetrans HF-2 (MYPE2120), Mycoplasma pulmonis UAB CTIP (MYPU_4070), Thermoanaerobacter tengcongensis MB4 (TTE2209), Pediococcus pentosaceus ATCC 25745 (PEPE_0475), Bacillus licheniformis DSM 13=ATCC 14580 2 seqs YBBP, BL02701), Staphylococcus haemolyticus JCSC1435 (SH0877), Desulfuromonas acetoxidans DSM 684 (DACE_0543), Thermodesulfovibrio yellowstonii DSM 11347 (THEYE_A0044), Mycoplasma bovis PG45 (MBOVPG45_0394), Anaeromyxobacter dehalogenans 2CP-C(ADEH_1497), Clostridium beijerinckii NCIMB 8052 (CBEI_0200), Borrelia garinii PBi (BG0008), Symbiobacterium thermophilum IAM 14863 (STH192), Alkaliphilus metalliredigens QYMF (AMET_4313), Thermus thermophilus HB8 (TTHA0323), Coprothermobacter proteolyticus DSM 5265 (COPRO5265_1086), Thermomicrobium roseum DSM 5159 (TRD_0688), Salinibacter ruber DSM 13855 (SRU_1946), Dokdonia donghaensis MED134 (MED134_03354), Polaribacter irgensii 23-P (PI23P_01632), Psychroflexus torquis ATCC 700755 (P700755_02202), Robiginitalea biformata HTCC2501 (RB2501_10597), Polaribacter sp. MED152 (MED152_11519), Maribacter sp. HTCC2170 (FB2170_01652), Microscilla marina ATCC 23134 (M23134_07024), Lyngbya sp. PCC 8106 (L8106_18951), Nodularia spumigena CCY9414 (N9414_23393), Synechococcus sp. BL107 (BL107_11781), Bacillus sp. NRRL B-14911 (B14911_19485), Lentisphaera araneosa HTCC2155 (LNTAR_18800), Lactobacillus sakei subsp. sakei 23K (LCA_1359), Mariprofundus ferrooxydans PV-1 (SPV1_13417), Borrelia hermsii DAH (BH0008), Borrelia turicatae 91E135 (BT0008), Bacillus weihenstephanensis KBAB4 (BCERKBAB4_0149), Bacillus cytotoxicus NVH 391-98 (BCER98_0148), Bacillus pumilus SAFR-032 (YBBP), Geobacter sp. FRC-32 2 seqs GEOB_2309, GEOB_3421), Herpetosiphon aurantiacus DSM 785 (HAUR_3416), Synechococcus sp. RCC307 (SYNRCC307_0791), Synechococcus sp. CC9902 (SYNCC9902_1392), Deinococcus geothermalis DSM 11300 (DGEO_0135), Synechococcus sp. PCC 7002 (SYNPCC7002_A0098), Synechococcus sp. WH 7803 (SYNWH7803_1532), Pedosphaera parvula Ellin514 (CFLAV_PD5552), Synechococcus sp. JA-3-3Ab (CYA_2894), Synechococcus sp. JA-2-3Ba(2-13) (CYB_1645), Aster yellows witches-broom phytoplasma AYWB (AYWB_243), Paenibacillus sp. JDR-2 (PJDR2_5631), Chloroflexus aurantiacus J-10-fl (CAUR_1577), Lactobacillus gasseri ATCC 33323 (LGAS_1288), Bacillus amyloliquefaciens FZB42 (YBBP), Chloroflexus aggregans DSM 9485 (CAGG_2337), Acaryochloris marina MBIC11017 (AM1_0413), Blattabacterium sp. (Blattella germanica) str. Bge (BLBBGE_101), Simkania negevensis Z (YBBP), Chlamydophila pecorum E58 (G5S_1046), Chlamydophila psittaci 6BC 2 seqs CPSIT_0714, G50_0707), Carnobacterium sp. AT7 (CAT7_06573), Finegoldia magna ATCC 29328 (FMG_1225), Syntrophomonas wolfei subsp. wolfei str. Goettingen (SWOL_2103), Syntrophobacter fumaroxidans MPOB (SFUM_3455), Pelobacter carbinolicus DSM 2380 (PCAR_0999), Pelobacter propionicus DSM 2379 2 seqs PPRO_2640, PPRO_2254), Thermoanaerobacter pseudethanolicus ATCC 33223 (TETH39_0457), Victivallis vadensis ATCC BAA-548 (VVAD_PD2437), Staphylococcus saprophyticus subsp. saprophyticus ATCC 15305 (SSP0722), Bacillus coagulans 36D1 (BCOA_1105), Mycoplasma hominis ATCC 23114 (MHO_0510), Lactobacillus reuteri 100-23 (LREU23DRAFT_3463), Desulfotomaculum reducens MI-1 (DRED_0292), Leuconostoc citreum KM20 (LCK_01297), Paenibacillus polymyxa E681 (PPE_04217), Akkermansia muciniphila ATCC BAA-835 (AMUC_0400), Alkaliphilus oremlandii OhILAs (CLOS_2417), Geobacter uraniireducens Rf4 2 seqs GURA_1367, GURA_2732), Caldicellulosiruptor saccharolyticus DSM 8903 (CSAC_1183), Pyramidobacter piscolens W5455 (HMPREF7215_0074), Leptospira borgpetersenii serovar Hardjo-bovis L550 (LBL_0913), Roseiflexus sp. RS-1 (ROSERS_1145), Clostridium phytofermentans ISDg (CPHY_3551), Brevibacillus brevis NBRC 100599 (BBR47_02670), Exiguobacterium sp. AT1b (EAT1B_1593), Lactobacillus salivarius UCC118 (LSL_1146), Lawsonia intracellularis PHE/MN1-00 (LI0190), Streptococcus mitis B6 (SMI_1552), Pelotomaculum thermopropionicum SI (PTH_0536), Streptococcus pneumoniae D39 (SPD_1392), Candidatus Phytoplasma mali (ATP_00312), Gemmatimonas aurantiaca T-27 (GAU_1394), Hydrogenobaculum sp. Y04AAS1 (HY04AAS1_0006), Roseiflexus castenholzii DSM 13941 (RCAS_3986), Listeria welshimeri serovar 6b str. SLCC5334 (LWE2139), Clostridium novyi NT (NTOICX_1162), Lactobacillus brevis ATCC 367 (LVIS_0684), Bacillus sp. B14905 (BB14905_08668), Algoriphagus sp. PR1 (ALPR1_16059), Streptococcus sanguinis SK36 (SSA_0802), Borrelia afzelii PKo 2 seqs BAPKO_0007, AEL69242.1), Lactobacillus delbrueckii subsp. bulgaricus ATCC 11842 (LDB0651), Streptococcus suis 05ZYH33 (SSU05_1470), Kordia algicida OT-1 (KAOT1_10521), Pedobacter sp. BAL39 (PBAL39_03944), Flavobacteriales bacterium ALC-1 (FBALC1_04077), Cyanothece sp. CCY0110 (CY0110_30633), Plesiocystis pacifica SIR-1 (PPSIR1_10140), Clostridium cellulolyticum H10 (CCEL_1201), Cyanothece sp. PCC 7425 (CYAN7425_4701), Staphylococcus carnosus subsp. carnosus TM300 (SCA_1665), Bacillus pseudofirmus OF4 (YBBP), Leeuwenhoekiella blandensis MED217 (MED217_04352), Geobacter lovleyi SZ 2 seqs GLOV_3055, GLOV_2524), Streptococcus equi subsp. zooepidemicus (SEZ_1213), Thermosinus carboxydivorans Nor (TCARDRAFT_1045), Geobacter bemidjiensis Bem (GBEM_0895), Anaeromyxobacter sp. Fw109-5 (ANAE109_2336), Lactobacillus helveticus DPC 4571 (LHV_0757), Bacillus sp. m3-13 (BM3-1_010100010851), Gramella forsetii KT0803 (GFO_0428), Ruminococcus obeum ATCC 29174 (RUMOBE_03597), Ruminococcus torques ATCC 27756 (RUMTOR_00870), Dorea formicigenerans ATCC 27755 (DORFOR_00204), Dorea longicatena DSM 13814 (DORLON_01744), Eubacterium ventriosum ATCC 27560 (EUBVEN_01080), Desulfovibrio piger ATCC 29098 (DESPIG_01592), Parvimonas micra ATCC 33270 (PEPMIC_01312), Pseudoflavonifractor capillosus ATCC 29799 (BACCAP_01950), Clostridium scindens ATCC 35704 (CLOSCI_02389), Eubacterium hallii DSM 3353 (EUBHAL_01228), Ruminococcus gnavus ATCC 29149 (RUMGNA_03537), Subdoligranulum variabile DSM 15176 (SUBVAR_05177), Coprococcus eutactus ATCC 27759 (COPEUT_01499), Bacteroides ovatus ATCC 8483 (BACOVA_03480), Parabacteroides merdae ATCC 43184 (PARMER_03434), Faecalibacterium prausnitzii A2-165 (FAEPRAA2165_01954), Clostridium sp. L2-50 (CLOL250_00341), Anaerostipes caccae DSM 14662 (ANACAC_00219), Bacteroides caccae ATCC 43185 (BACCAC_03225), Clostridium bolteae ATCC BAA-613 (CLOBOL_04759), Borrelia duttonii Ly (BDU_14), Cyanothece sp. PCC 8801 (PCC8801_0127), Lactococcus lactis subsp. cremoris MG1363 (LLMG_0448), Geobacillus thermodenitrificans NG80-2 (GTNG_0149), Epulopiscium sp. N.t. morphotype B (EPULO_010100003839), Lactococcus garvieae Lg2 (LCGL_0304), Clostridium leptum DSM 753 (CLOLEP_03097), Clostridium spiroforme DSM 1552 (CLOSPI_01608), Eubacterium dolichum DSM 3991 (EUBDOL_00188), Clostridium kluyveri DSM 555 (CKL_0313), Porphyromonas gingivalis ATCC 33277 (PGN_0523), Bacteroides vulgatus ATCC 8482 (BVU_0518), Parabacteroides distasonis ATCC 8503 (BDI_3368), Staphylococcus hominis subsp. hominis C80 (HMPREF0798_01968), Staphylococcus caprae C87 (HMPREF0786_02373), Streptococcus sp. C150 (HMPREF0848_00423), Sulfurihydrogenibium sp. YO3AOP1 (SYO3AOP1_0110), Desulfatibacillum alkenivorans AK-01 (DALK_0397), Bacillus selenitireducens MLS10 (BSEL_0372), Cyanothece sp. ATCC 51142 (CCE_1350), Lactobacillus jensenii 1153 (LBJG_01645), Acholeplasma laidlawii PG-8A (ACL_1368), Bacillus coahuilensis m4-4 (BCOAM_010100001120), Geobacter sp. M18 2 seqs GM18_0792, GM18_2516), Lysinibacillus sphaericus C3-41 (BSPH_4568), Clostridium botulinum NCTC 2916 (CBN_3506), Clostridium botulinum C str. Eklund (CBC_A1575), Alistipes putredinis DSM 17216 (ALIPUT_00190), Anaerofustis stercorihominis DSM 17244 (ANASTE_01539), Anaerotruncus colihominis DSM (ANACOL_02706), Clostridium bartlettii DSM 16795 (CLOBAR_00759), Clostridium ramosum DSM 1402 (CLORAM_01482), Borrelia valaisiana VS116 (BVAVS116_0007), Sorangium cellulosum So ce 56 (SCE7623), Microcystis aeruginosa NIES-843 (MAE_25390), Bacteroides stercoris ATCC 43183 (BACSTE_02634), Candidatus Amoebophilus asiaticus 5a2 (AASI_0652), Leptospira biflexa serovar Patoc strain Patoc 1 (Paris) (LEPBI_I0735), Clostridium sp. 7_2_43FAA (CSBG_00101), Desulfovibrio sp. 3_1_syn3 (HMPREF0326_02254), Ruminococcus sp. 5_1_39BFAA (RSAG_02135), Clostridiales bacterium 1_7_47FAA (CBFG_00347), Bacteroides fragilis 3_1_12 (BFAG_02578), Natranaerobius thermophilus

JW/NM-WN-LF (NTHER_0240), Macrococcus caseolyticus JCSC5402 (MCCL_0321), Streptococcus gordonii str. Challis substr. CH1 (SGO_0887), Dethiosulfovibrio peptidovorans DSM 11002 (DPEP_2062), Coprobacillus sp. 29_1 (HMPREF9488_03448), Bacteroides coprocola DSM 17136 (BACCOP_03665), Coprococcus comes ATCC 27758 (COPCOM_02178), Geobacillus sp. WCH70 (GWCH70_0156), uncultured Termite group 1 bacterium phylotype Rs-D17 (TGRD_209), Dyadobacter fermentans DSM 18053 (DFER_0224), Bacteroides intestinalis DSM 17393 (BACINT_00700), Ruminococcus lactaris ATCC 29176 (RUMLAC_01257), Blautia hydrogenotrophica DSM 10507 (RUMHYD_01218), Candidatus Desulforudis audaxviator MP104C (DAUD_1932), Marvinbryantia formatexigens DSM 14469 (BRYFOR_07410), Sphaerobacter thermophilus DSM 20745 (STHE_1601), Veillonella parvula DSM 2008 (VPAR_0292), Methylacidiphilum infernorum V4 (MINF_1897), Paenibacillus sp. Y412MC10 (GYMC10_5701), Bacteroides finegoldii DSM 17565 (BACFIN_07732), Bacteroides eggerthii DSM 20697 (BACEGG_03561), Bacteroides pectinophilus ATCC 43243 (BACPEC_02936), Bacteroides plebeius DSM 17135 (BACPLE_00693), Desulfohalobium retbaense DSM 5692 (DRET_1725), Desulfotomaculum acetoxidans DSM 771 (DTOX_0604), Pedobacter heparinus DSM 2366 (PHEP_3664), Chitinophaga pinensis DSM 2588 (CPIN_5466), Flavobacteria bacterium MS024-2A (FLAV2ADRAFT_0090), Flavobacteria bacterium MS024-3C (FLAV3CDRAFT_0851), Moorea producta 3L (LYNGBM3L_14400), Anoxybacillus flavithermus WK1 (AFLV_0149), Mycoplasma fermentans PG18 (MBIO_0474), Chthoniobacter flavus Ellin428 (CFE428DRAFT_3031), Cyanothece sp. PCC 7822 (CYAN7822_1152), Borrelia spielmanii A14S (BSPA14S_0009), Heliobacterium modesticaldum Icel (HM1_1522), Thermus aquaticus Y51MC23 (TAQDRAFT_3938), Clostridium sticklandii DSM 519 (CLOST_0484), Tepidanaerobacter sp. Rel (TEPRE1_0323), Clostridium hiranonis DSM 13275 (CLOHIR_00003), Mitsuokella multacida DSM 20544 (MITSMUL_03479), Haliangium ochraceum DSM 14365 (HOCH_3550), Spirosoma linguale DSM 74 (SLIN_2673), unidentified eubacterium SCB49 (SCB49_03679), Acetivibrio cellulolyticus CD2 (ACELC_020100013845), Lactobacillus buchneri NRRL B-30929 (LBUC_1299), Butyrivibrio crossotus DSM 2876 (BUTYVIB_02056), Candidatus Azobacteroides pseudotrichonymphae genomovar. CFP2 (CFPG_066), Mycoplasma crocodyli MP145 (MCRO_0385), Arthrospira maxima CS-328 (AMAXDRAFT_4184), Eubacterium eligens ATCC 27750 (EUBELI_01626), Butyrivibrio proteoclasticus B316 (BPR_I2587), Chloroherpeton thalassium ATCC 35110 (CTHA_1340), Eubacterium biforme DSM 3989 (EUBIFOR_01794), Rhodothermus marinus DSM 4252 (RMAR_0146), Borrelia bissettii DN127 (BBIDN127_0008), Capnocytophaga ochracea DSM 7271 (COCH_2107), Alicyclobacillus acidocaldarius subsp. acidocaldarius DSM 446 (AACI_2672), Caldicellulosiruptor bescii DSM 6725 (ATHE_0361), Denitrovibrio acetiphilus DSM 12809 (DACET_1298), Desulfovibrio desulfuricans subsp. desulfuricans str. ATCC 27774 (DDES_1715), Anaerococcus lactolyticus ATCC 51172 (HMPREF0072_1645), Anaerococcus tetradius ATCC 35098 (HMPREF0077_0902), Finegoldia magna ATCC 53516 (HMPREF0391_10377), Lactobacillus antri DSM 16041 (YBBP), Lactobacillus buchneri ATCC 11577 (HMPREF0497_2752), Lactobacillus ultunensis DSM 16047 (HMPREF0548_0745), Lactobacillus vaginalis ATCC 49540 (HMPREF0549_0766), Listeria grayi DSM 20601 (HMPREF0556_11652), Sphingobacterium spiritivorum ATCC 33861 (HMPREF0766_11787), Staphylococcus epidermidis M23864:W1 (HMPREF0793_0092), Streptococcus equinus ATCC 9812 (HMPREF0819_0812), Desulfomicrobium baculatum DSM 4028 (DBAC_0255), Thermanaerovibrio acidaminovorans DSM 6589 (TACI_0837), Thermobaculum terrenum ATCC BAA-798 (TTER_1817), Anaerococcus prevotii DSM 20548 (APRE_0370), Desulfovibrio salexigens DSM 2638 (DESAL_1795), Brachyspira murdochii DSM 12563 (BMUR_2186), Meiothermus silvanus DSM 9946 (MESIL_0161), Bacillus cereus Rock4-18 (BCERE0024_1410), Cylindrospermopsis raciborskii CS-505 (CRC_01921), Raphidiopsis brookii D9 (CRD_01188), Clostridium carboxidivorans P7 2 seqs CLCAR_0016, CCARBDRAFT_4266), Clostridium botulinum E1 str. BoNT E Beluga (CLO_3490), Blautia hansenii DSM 20583 (BLAHAN_07155), Prevotella copri DSM 18205 (PREVCOP_04867), Clostridium methylpentosum DSM 5476 (CLOSTMETH_00084), Lactobacillus casei BL23 (LCABL_11800), Bacillus megaterium QM B1551 (BMQ_0195), Treponema primitia ZAS-2 (TREPR_1936), Treponema azotonutricium ZAS-9 (TREAZ_0147), Holdemania filiformis DSM 12042 (HOLDEFILI_03810), Filifactor alocis ATCC 35896 (HMPREF0389_00366), Gemella haemolysans ATCC 10379 (GEMHA0001_0912), Selenomonas sputigena ATCC 35185 (SELSP_1610), Veillonella dispar ATCC 17748 (VEIDISOL_01845), Deinococcus deserti VCD115 (DEIDE_19700), Bacteroides coprophilus DSM 18228 (BACCOPRO_00159), Nostoc azollae 0708 (AAZO_4735), Erysipelotrichaceae bacterium 5_2_54FAA (HMPREF0863_02273), Ruminococcaceae bacterium D16 (HMPREF0866_01061), Prevotella bivia JCVIHMP010 (HMPREF0648_0338), Prevotella melaninogenica ATCC 25845 (HMPREF0659_A6212), Porphyromonas endodontalis ATCC 35406 (POREN0001_0251), Capnocytophaga sputigena ATCC 33612 (CAPSP0001_0727), Capnocytophaga gingivalis ATCC 33624 (CAPGI0001_1936), Clostridium hylemonae DSM 15053 (CLOHYLEM_04631), Thermosediminibacter oceani DSM 16646 (TOCE_1970), Dethiobacter alkaliphilus AHT 1 (DEALDRAFT_0231), Desulfonatronospira thiodismutans AS03-1 (DTHIO_PD2806), Clostridium sp. D5 (HMPREF0240_03780), Anaerococcus hydrogenalis DSM 7454 (ANHYDRO_01144), Kyrpidia tusciae DSM 2912 (BTUS_0196), Gemella haemolysans M341 (HMPREF0428_01429), Gemella morbillorum M424 (HMPREF0432_01346), Gemella sanguinis M325 (HMPREF0433_01225), Prevotella oris C735 (HMPREF0665_01741), Streptococcus sp. M143 (HMPREF0850_00109), Streptococcus sp. M334 (HMPREF0851_01652), Bilophila wadsworthia 3_1_6 (HMPREF0179_00899), Brachyspira hyodysenteriae WA1 (BHWA1_01167), Enterococcus gallinarum EG2 (EGBG_00820), Enterococcus casseliflavus EC20 (ECBG_00827), Enterococcus faecium C68 (EFXG_01665), Syntrophus aciditrophicus SB (SYN_02762), Lactobacillus rhamnosus GG 2 seqs OSSG, LRHM_0937), Acidaminococcus intestini RyC-MR95 (ACIN_2069), Mycoplasma conjunctivae HRC/581 (MCJ_002940), Halanaerobium praevalens DSM 2228 (HPRAE_1647), Aminobacterium colombiense DSM 12261 (AMICO_0737), Clostridium cellulovorans 743B (CLOCEL_3678), Desulfovibrio magneticus RS-1 (DMR_25720), Spirochaeta smaragdinae DSM 11293 (SPIRS_1647), Bacteroidetes oral taxon 274 str. F0058 (HMPREF0156_01826), Lachnospiraceae oral taxon 107 str. F0167 (HMPREF0491_01238), Lactobacillus coleohominis 101-4-CHN (HMPREF0501_01094), Lactobacillus jensenii 27-2-CHN (HMPREF0525_00616), Prevotella buccae D17 (HMPREF0649_02043), Prevotella sp. oral taxon 299 str. F0039 (HMPREF0669_01041), Prevotella sp. oral taxon 317 str. F0108 (HMPREF0670_02550), Desulfobulbus propionicus DSM 2032 2 seqs DESPR_2503, DESPR_1053), Thermoanaerobacterium thermosaccharolyticum DSM 571 (TTHE_0484), Thermoanaerobacter italicus Ab9 (THIT_1921), Thermovirga lienii DSM 17291 (TLIE_0759), Aminomonas paucivorans DSM 12260 (APAU_1274), Streptococcus mitis SK321 (SMSK321_0127), Streptococcus mitis SK597 (SMSK597_0417), Roseburia hominis A2-183 (RHOM_12405), Oribacterium sinus F0268 (HMPREF6123_0887), Prevotella bergensis DSM 17361 (HMPREF0645_2701), Selenomonas noxia ATCC 43541 (YBBP), Weissella paramesenteroides ATCC 33313 (HMPREF0877_0011), Lactobacillus amylolyticus DSM 11664 (HMPREF0493_1017), Bacteroides sp. D20 (HMPREF0969_02087), Clostridium papyrosolvens DSM 2782 (CPAP_3968), Desulfurivibrio alkaliphilus AHT2 (DAAHT2_0445), Acidaminococcus fermentans DSM 20731 (ACFER_0601), Abiotrophia defectiva ATCC 49176 (GCWU000182_00063), Anaerobaculum hydrogeniformans ATCC BAA-1850 (HMPREF1705_01115), Catonella morbi ATCC 51271 (GCWU000282_00629), Clostridium botulinum D str. 1873 (CLG_B1859), Dialister invisus DSM 15470 (GCWU000321_01906), Fibrobacter succinogenes subsp. succinogenes S85 2 seqs FSU_0028, FISUC_2776), Desulfovibrio fructosovorans JJ (DESFRDRAFT_2879), Peptostreptococcus stomatis DSM 17678 (HMPREF0634_0727), Staphylococcus warneri L37603 (STAWA0001_0094), Treponema vincentii ATCC 35580 (TREVI00011289), Porphyromonas uenonis 60-3 (PORUE0001_0199), Peptostreptococcus anaerobius 653-L (HMPREF0631_1228), Peptoniphilus lacrimalis 315-B (HMPREF0628_0762), Candidatus Phytoplasma australiense (PA0090), Prochlorococcus marinus subsp. pastoris str. CCMP1986 (PMM1091), Synechococcus sp. WH 7805 (WH7805_04441), Blattabacterium sp. (Periplaneta americana) str. BPLAN (BPLAN_534), Caldicellulosiruptor obsidiansis OB47 (COB47_0325), Oribacterium sp. oral taxon 078 str. F0262 (GCWU000341_01365), Hydrogenobacter thermophilus TK-6 2 seqs AD046034.1, HTH_1665), Clostridium saccharolyticum WM1 (CLOSA_1248), Prevotella sp. oral taxon 472 str. F0295 (HMPREF6745_1617), Paenibacillus sp. oral taxon 786 str. D14 (POTG_03822), Roseburia inulinivorans DSM 16841 2 seqs ROSEINA2194_02614, ROSEINA2194_02613), Granulicatella elegans ATCC 700633 (HMPREF0446_01381), Prevotella tannerae ATCC 51259 (GCWU000325_02844), Shuttleworthia satelles DSM 14600 (GCWU000342_01722), Phascolarctobacterium succinatutens YIT 12067 (HMPREF9443_01522), Clostridium butyricum E4 str. BoNT E BL5262 (CLP_3980), Caldicellulosiruptor hydrothermalis 108 (CALHY_2287), Caldicellulosiruptor kristjanssonii 177R1B (CALKR_0314), Caldicellulosiruptor owensensis OL (CALOW_0228), Eubacterium cellulosolvens 6 (EUBCEDRAFT_1150), Geobacillus thermoglucosidasius C56-YS93 (GEOTH_0175), Thermincola potens JR (THERJR_0376), Nostoc punctiforme PCC 73102 (NPUN_F5990), Granulicatella adiacens ATCC 49175 (YBBP), Selenomonas flueggei ATCC 43531 (HMPREF0908_1366), Thermocrinis albus DSM 14484 (THAL_0234), Deferribacter desulfuricans SSM1 (DEFDS_1031), Ruminococcus flavefaciens FD-1 (RFLAF_010100012444), Desulfovibrio desulfuricans ND132 (DND132_0877), Clostridium lentocellum DSM 5427 (CLOLE_3370), Desulfovibrio aespoeensis Aspo-2 (DAES_1257), Syntrophothermus lipocalidus DSM 12680 (SLIP_2139), Marivirga tractuosa DSM 4126 (FTRAC_3720), Desulfarculus baarsii DSM 2075 (DEBA_0764), Synechococcus sp. CC9311 (SYNC_1030), Thermaerobacter marianensis DSM 12885 (TMAR_0236), Desulfovibrio sp. FW1012B (DFW101_0480), Jonquetella anthropi E3_33 E1 (GCWU000246_01523), Syntrophobotulus glycolicus DSM 8271 (SGLY_0483), Thermovibrio ammonificans HB-1 (THEAM_0892), Truepera radiovictrix DSM 17093 (TRAD_1704), Bacillus cellulosilyticus DSM 2522 (BCELL_0170), Prevotella veroralis F0319 (HMPREF0973_02947), Erysipelothrix rhusiopathiae str. Fujisawa (ERH_0115), Desulfurispirillum indicum S5 (SELIN_2326), Cyanothece sp. PCC 7424 (PCC7424_0843), Anaerococcus vaginalis ATCC 51170 (YBBP), Aerococcus viridans ATCC 11563 (YBBP), Streptococcus oralis ATCC 35037 2 seqs HMPREF8579_1682, SMSK23_1115), Zunongwangia profunda SM-A87 (ZPR_0978), Halanaerobium hydrogeniformans (HALSA_1882), Bacteroides xylanisolvens XB1A (BXY_29650), Ruminococcus torques L2-14 (RTO_16490), Ruminococcus obeum A2-162 (CK5_33600), Eubacterium rectale DSM 17629 (EUR_24910), Faecalibacterium prausnitzii SL3/3 (FPR_27630), Ruminococcus sp. SRI/5 (CK1_39330), Lachnospiraceae bacterium 3_1_57FAA_CT1 (HMPREF0994_01490), Lachnospiraceae bacterium 9_1_43BFAA (HMPREF0987_01591), Lachnospiraceae bacterium 1_4_56FAA (HMPREF0988_01806), Erysipelotrichaceae bacterium 3_1_53 (HMPREF0983_01328), Ethanoligenens harbinense YUAN-3 (ETHHA_1605), Streptococcus dysgalactiae subsp. dysgalactiae ATCC 27957 (SDD27957_06215), Spirochaeta thermophila DSM 6192 (STHERM_C18370), Bacillus sp. 2_A_57_CT2 (HMPREF1013_05449), Bacillus clausii KSM-K16 (ABC0241), Thermodesulfatator indicus DSM 15286 (THEIN_0076), Bacteroides salanitronis DSM 18170 (BACSA_1486), Oceanithermus profundus DSM 14977 (OCEPR_2178), Prevotella timonensis CRIS 5C-B1 (HMPREF9019_2028), Prevotella buccalis ATCC 35310 (HMPREF0650_0675), Prevotella amnii CRIS 21A-A (HMPREF9018_0365), Bulleidia extructa W1219 (HMPREF9013_0078), Bacteroides coprosuis DSM 18011 (BCOP_0558), Prevotella multisaccharivorax DSM 17128 (PREMU_0839), Cellulophaga algicola DSM 14237 (CELAL_0483), Synechococcus sp. WH 5701 (WH5701_10360), Desulfovibrio africanus str. Walvis Bay (DESAF_3283), Oscillibacter valericigenes Sjm18-20 (OBV_23340), Deinococcus proteolyticus MRP (DEIPR_0134), Bacteroides helcogenes P 36-108 (BACHE_0366), Paludibacter propionicigenes WB4 (PALPR_1923), Desulfotomaculum nigrificans DSM 574 (DESNIDRAFT_2093), Arthrospira platensis NIES-39 (BAI89442.1), Mahella australiensis 50-1 BON (MAHAU_1846), Thermoanaerobacter wiegelii Rt8.B1 (THEWI_2191), Ruminococcus albus 7 (RUMAL_2345), Staphylococcus lugdunensis HKU09-01 (SLGD_00862), Megasphaera genomosp. type_1 str. 28L (HMPREF0889_1099), Clostridiales genomosp. BVAB3 str. UPII9-5 (HMPREF0868_1453), Pediococcus claussenii ATCC BAA-344 (PECL_571), Prevotella oulorum F0390 (HMPREF9431_01673), Turicibacter sanguinis PC909 (CUW_0305), Listeria seeligeri FSL N1-067 (NT03LS_2473), Solobacterium moorei F0204 (HMPREF9430_01245), Megasphaera micronuciformis F0359 (HMPREF9429_00929), Capnocytophaga sp. oral taxon 329 str. F0087 2 seqs HMPREF9074_00867, HMPREF9074_01078), Streptococcus anginosus F0211 (HMPREF0813_00157), Mycoplasma suis KI3806 (MSUI04040), Mycoplasma gallisepticum str. F (MGF_2771), Deinococcus maricopensis DSM 21211 (DEIMA_0651), Odoribacter splanchnicus DSM 20712 (ODOSP_0239), Lactobacillus fermentum CECT 5716 (LC40_0265), Lactobacillus iners AB-1 (LINEA_010100006089), cyanobacterium UCYN-A (UCYN_03150), Lactobacillus sanfranciscensis TMW 1.1304 (YBBP), Mucilaginibacter paludis DSM 18603 (MUCPA_1296), Lysinibacillus fusiformis ZC1 (BFZC1_03142), Paenibacillus vortex V453 (PVOR_30878), Waddlia chondrophila WSU 86-1044 (YBBP), Flexistipes sinusarabici DSM 4947 (FLEXSI_0971), Paenibacillus curdlanolyticus YK9 (PAECUDRAFT_1888), Clostridium cf. saccharolyticum K10 (CLS_03290), Alistipes shahii WAL 8301 (AL1_02190), Eubacterium cylindroides T2-87 (EC1_00230), Coprococcus catus GD/7 (CC1_32460), Faecalibacterium prausnitzii L2-6 (FP2_09960), Clostridium clariflavum DSM 19732 (CLOCL_2983), Bacillus atrophaeus 1942 (BATR1942_19530), Mycoplasma pneumoniae FH (MPNE_0277), Lachnospiraceae bacterium 2_1_46FAA (HMPREF9477_00058), Clostridium symbiosum WAL-14163 (HMPREF9474_01267), Dysgonomonas gadei ATCC BAA-286 (HMPREF9455_02764), Dysgonomonas mossii DSM 22836 (HMPREF9456_00401), Thermus scotoductus SA-01 (TSC_C24350), Sphingobacterium sp. 21 (SPH21_1233), Spirochaeta caldaria DSM 7334 (SPICA_1201), Prochlorococcus marinus str. MIT 9312 (PMT9312_1102), Prochlorococcus marinus str. MIT 9313 (PMT_1058), Faecalibacterium cf. prausnitzii KLE1255 (HMPREF9436_00949), Lactobacillus crispatus ST1 (LCRIS_00721), Clostridium ljungdahlii DSM 13528 (CLJU_C40470), Prevotella bryantii B14 (PBR_2345), Treponema phagedenis F0421 (HMPREF9554_02012), Clostridium sp. BNL1100 (CLO1100_2851), Microcoleus vaginatus FGP-2 (MICVADRAFT_1377), Brachyspira pilosicoli 95/1000 (BP951000_0671), Spirochaeta coccoides

DSM 17374 (SPICO_1456), Haliscomenobacter hydrossis DSM 1100 (HALHY_5703), Desulfotomaculum kuznetsovii DSM 6115 (DESKU_2883), Runella slithyformis DSM 19594 (RUNSL_2859), Leuconostoc kimchii IMSNU 11154 (LKI_08080), Leuconostoc gasicomitatum LMG 18811 (OSSG), Pedobacter saltans DSM 12145 (PEDSA_3681), Paraprevotella xylaniphila YIT 11841 (HMPREF9442_00863), Bacteroides clarus YIT 12056 (HMPREF9445_01691), Bacteroides fluxus YIT 12057 (HMPREF9446_03303), Streptococcus urinalis 2285-97 (STRUR_1376), Streptococcus macacae NCTC 11558 (STRMA_0866), Streptococcus ictaluri 707-05 (STRIC_0998), Oscillochloris trichoides DG-6 (OSCT_2821), Parachlamydia acanthamoebae UV-7 (YBBP), Prevotella denticola F0289 (HMPREF9137_0316), Parvimonas sp. oral taxon 110 str. F0139 (HMPREF9126_0534), Calditerrivibrio nitroreducens DSM 19672 (CALNI_1443), Desulfosporosinus orientis DSM 765 (DESOR_0366), Streptococcus mitis bv. 2 str. F0392 (HMPREF9178_0602), Thermodesulfobacterium sp. OPB45 (TOPB45_1366), Synechococcus sp. WH 8102 (SYNW0935), Thermoanaerobacterium xylanolyticum LX-11 (THEXY_0384), Mycoplasma haemofelis Ohio2 (MHF_1192), Capnocytophaga canimorsus Cc5 (CCAN_16670), Pediococcus acidilactici DSM 20284 (HMPREF0623_1647), Prevotella marshii DSM 16973 (HMPREF0658_1600), Peptoniphilus duerdenii ATCC BAA-1640 (HMPREF9225_1495), Bacteriovorax marinus SJ (BMS_2126), Selenomonas sp. oral taxon 149 str. 67H29BP (HMPREF9166_2117), Eubacterium yurii subsp. margaretiae ATCC 43715 (HMPREF0379_1170), Streptococcus mitis ATCC 6249 (HMPREF8571_1414), Streptococcus sp. oral taxon 071 str. 73H25AP (HMPREF9189_0416), Prevotella disiens FB035-09AN (HMPREF9296_1148), Aerococcus urinae ACS-120-V-Col10a (HMPREF9243_0061), Veillonella atypica ACS-049-V-Sch6 (HMPREF9321_0282), Cellulophaga lytica DSM 7489 (CELLY_2319), Thermaerobacter subterraneus DSM 13965 (THESUDRAFT_0411), Desulfurobacterium thermolithotrophum DSM 11699 (DESTER_0391), Treponema succinifaciens DSM 2489 (TRESU_1152), Marinithermus hydrothermalis DSM 14884 (MARKY_1861), Streptococcus infantis SK1302 (SIN_0824), Streptococcus parauberis NCFD 2020 (SPB_0808), Streptococcus porcinus str. Jelinkova 176 (STRPO_0164), Streptococcus criceti HS-6 (STRCR_1133), Capnocytophaga ochracea F0287 (HMPREF1977_0786), Prevotella oralis ATCC 33269 (HMPREF0663_10671), Porphyromonas asaccharolytica DSM 20707 (PORAS_0634), Anaerococcus prevotii ACS-065-V-Col13 (HMPREF9290_0962), Peptoniphilus sp. oral taxon 375 str. F0436 (HMPREF9130_1619), Veillonella sp. oral taxon 158 str. F0412 (HMPREF9199_0189), Selenomonas sp. oral taxon 137 str. F0430 (HMPREF9162_2458), Cyclobacterium marinum DSM 745 (CYCMA_2525), Desulfobacca acetoxidans DSM 11109 (DESAC_1475), Listeria ivanovii subsp. ivanovii PAM 55 (LIV_2111), Desulfovibrio vulgaris str. Hildenborough (DVU_1280), Desulfovibrio vulgaris str. `Miyazaki F` (DVMF_0057), Muricauda ruestringensis DSM 13258 (MURRU_0474), Leuconostoc argentinum KCTC 3773 (LARGK3_010100008306), Paenibacillus polymyxa SC2 (PPSC2_C4728), Eubacterium saburreum DSM 3986 (HMPREF0381_2518), Pseudoramibacter alactolyticus ATCC 23263 (HMP0721_0313), Streptococcus parasanguinis ATCC 903 (HMPREF8577_0233), Streptococcus sanguinis ATCC 49296 (HMPREF8578_1820), Capnocytophaga sp. oral taxon 338 str. F0234 (HMPREF9071_1325), Centipeda periodontii DSM 2778 (HMPREF9081_2332), Prevotella multiformis DSM 16608 (HMPREF9141_0346), Streptococcus peroris ATCC 700780 (HMPREF9180_0434), Prevotella salivae DSM 15606 (HMPREF9420_1402), Streptococcus australis ATCC 700641 2 seqs HMPREF9961_0906, HMPREF9421_1720), Streptococcus cristatus ATCC 51100 2 seqs HMPREF9422_0776, HMPREF9960_0531), Lactobacillus acidophilus 30SC (LAC30SC_03585), Eubacterium limosum KIST612 (ELI_0726), Streptococcus downei F0415 (HMPREF9176_1204), Streptococcus sp. oral taxon 056 str. F0418 (HMPREF9182_0330), Oribacterium sp. oral taxon 108 str. F0425 (HMPREF9124_1289), Streptococcus vestibularis F0396 (HMPREF9192_1521), Treponema brennaborense DSM 12168 (TREBR_1165), Leuconostoc fallax KCTC 3537 (LFALK3_010100008689), Eremococcus coleocola ACS-139-V-Col8 (HMPREF9257_0233), Peptoniphilus harei ACS-146-V-Sch2b (HMPREF9286_0042), Clostridium sp. HGF2 (HMPREF9406_3692), Alistipes sp. HGB5 (HMPREF9720_2785), Prevotella dentalis DSM 3688 (PREDE_0132), Streptococcus pseudoporcinus SPIN 20026 (HMPREF9320_0643), Dialister microaerophilus UPII 345-E (HMPREF9220_0018), Weissella cibaria KACC 11862 (WCIBK1_010100001174), Lactobacillus coryniformis subsp. coryniformis KCTC 3167 (LCORCK3_010100001982), Synechococcus sp. PCC 7335 (S7335_3864), Owenweeksia hongkongensis DSM 17368 (OWEHO_3344), Anaerolinea thermophila UNI-1 (ANT_09470), Streptococcus oralis Uo5 (SOR_0619), Leuconostoc gelidum KCTC 3527 (LGELK3_010100006746), Clostridium botulinum BKT015925 (CBC4_0275), Prochlorococcus marinus str. MIT 9211 (P9211_10951), Prochlorococcus marinus str. MIT 9215 (P9215_12271), Staphylococcus aureus subsp. aureus NCTC 8325 (SAOUHSC_02407), Staphylococcus aureus subsp. aureus COL (SACOL2153), Lactobacillus animalis KCTC 3501 (LANIK3_010100000290), Fructobacillus fructosus KCTC 3544 (FFRUK3_010100006750), Acetobacterium woodii DSM 1030 (AWO_C28200), Planococcus donghaensis MPA1U2 (GPDM_12177), Lactobacillus farciminis KCTC 3681 (LFARK3_010100009915), Melissococcus plutonius ATCC 35311 (MPTP_0835), Lactobacillus fructivorans KCTC 3543 (LFRUK3_010100002657), Paenibacillus sp. HGF7 (HMPREF9413_5563), Lactobacillus oris F0423 (HMPREF9102_1081), Veillonella sp. oral taxon 780 str. F0422 (HMPREF9200_1112), Parvimonas sp. oral taxon 393 str. F0440 (HMPREF9127_1171), Tetragenococcus halophilus NBRC 12172 (TEH_13100), Candidatus Chloracidobacterium thermophilum B (CABTHER_A1277), Ornithinibacillus scapharcae TW25 (OTW25_010100020393), Lacinutrix sp. 5H-3-7-4 (LACAL_0337), Krokinobacter sp. 4H-3-7-5 (KRODI_0177), Staphylococcus pseudintermedius ED99 (SPSE_0659), Staphylococcus aureus subsp. aureus MSHR1132 (CCE59824.1), Paenibacillus terrae HPL-003 (HPL003_03660), Caldalkalibacillus thermarum TA2.A1 (CATHTA2_0882), Desmospora sp. 8437 (HMPREF9374_2897), Prevotella nigrescens ATCC 33563 (HMPREF9419_1415), Prevotella pallens ATCC 700821 (HMPREF9144_0175), Streptococcus infantis X (HMPREF1124.

[0264] In some embodiments, the genetically engineered bacteria are capable of increasing c-di-AMP levels. In some embodiments, the genetically engineered bacteria are capable of increasing c-diAMP levels in the intracellular space. In some embodiments, the genetically engineered bacteria are capable of increasing c-diAMP levels inside of a eukaryotic cell. In some embodiments, the genetically engineered bacteria are capable of increasing c-diAMP levels inside of an immune cell. In some embodiments, the cell is a phagocyte. In some embodiments, the cell is a macrophage. In some embodiments, the cell is a dendritic cell. In some embodiments, the cell is a neutrophil. In some embodiments, the cell is a MDSC. In some embodiments, the genetically engineered bacteria are capable of increasing c-GAMP (2'3' or 3'3') and/or cyclic-di-GMP levels inside of a cell. In some embodiments, the genetically engineered bacteria are capable of increasing c-di-AMP levels in vitro in the bacterial cell and/or in the growth medium.

[0265] In any of these embodiments, the bacteria genetically engineered to produce cyclic-di-AMP produce at least about 0% to 2% to 4%, 4% to 6%, 6% to 8%, 8% to 10%, 10% to 12%, 12% to 14%, 14% to 16%, 16% to 18%, 18% to 20%, 20% to 25%, 25% to 30%, 30% to 35%, 35% to 40%, 40% to 45% 45% to 50%, 50% to 55%, 55% to 60%, 60% to 65%, 65% to 70% to 80%, 80% to 90%, or 90% to 100% more cyclic-di-AMP than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, the genetically engineered bacteria produce at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold more cyclic-di-AMP than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, the genetically engineered bacteria produce at least about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold or more cyclic-di-AMP than unmodified bacteria of the same bacterial subtype under the same conditions.

[0266] In any of these embodiments, the bacteria genetically engineered to produce cyclic-di-AMP consume at least about 0% to 2% to 4%, 4% to 6%, 6% to 8%, 8% to 10%, 10% to 12%, 12% to 14%, 14% to 16%, 16% to 18%, 18% to 20%, 20% to 25%, 25% to 30%, 30% to 35%, 35% to 40%, 40% to 45% 45% to 50%, 50% to 55%, 55% to 60%, 60% to 65%, 65% to 70% to 80%, 80% to 90%, or 90% to 100% more ATP than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, the genetically engineered bacteria consume at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold more ATP than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, the genetically engineered bacteria produce at least about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold or more cyclic-di-AMP than unmodified bacteria of the same bacterial subtype under the same conditions.

[0267] In any of these embodiments, the bacteria genetically engineered to produce cyclic-di-GAMP produce at least about 0% to 2% to 4%, 4% to 6%, 6% to 8%, 8% to 10%, 10% to 12%, 12% to 14%, 14% to 16%, 16% to 18%, 18% to 20%, 20% to 25%, 25% to 30%, 30% to 35%, 35% to 40%, 40% to 45% 45% to 50%, 50% to 55%, 55% to 60%, 60% to 65%, 65% to 70% to 80%, 80% to 90%, or 90% to 100% more arginine than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, the genetically engineered bacteria produce at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold more cyclic-di-GAMP than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, the genetically engineered bacteria produce at least about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold or more cyclic-di-GAMP than unmodified bacteria of the same bacterial subtype under the same conditions.

[0268] In any of these embodiments, the bacteria genetically engineered to produce cyclic-di-GAMP consume at least about 0% to 2% to 4%, 4% to 6%, 6% to 8%, 8% to 10%, 10% to 12%, 12% to 14%, 14% to 16%, 16% to 18%, 18% to 20%, 20% to 25%, 25% to 30%, 30% to 35%, 35% to 40%, 40% to 45% 45% to 50%, 50% to 55%, 55% to 60%, 60% to 65%, 65% to 70% to 80%, 80% to 90%, or 90% to 100% more ATP than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, the genetically engineered bacteria consume at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold more ATP and/or GTP than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, the genetically engineered bacteria consume at least about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold or more ATP and/or GTP than unmodified bacteria of the same bacterial subtype under the same conditions.

[0269] In any of these embodiments, the genetically engineered bacteria increase STING agonist production rate by at least about 0% to 2% to 4%, 4% to 6%, 6% to 8%, 8% to 10%, 10% to 12%, 12% to 14%, 14% to 16%, 16% to 18%, 18% to 20%, 20% to 25%, 25% to 30%, 30% to 35%, 35% to 40%, 40% to 45% 45% to 50%, 50% to 55%, 55% to 60%, 60% to 65%, 65% to 70% to 80%, 80% to 90%, or 90% to 100% relative to unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, the genetically engineered bacteria increase the STING agonist production rate by at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold more relative to unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, the genetically engineered bacteria increase STING agonist production rate by about three-fold, four-fold, five-fold, six-fold, seven-fold, eight-fold, nine-fold, ten-fold, fifteen-fold, twenty-fold, thirty-fold, forty-fold, or fifty-fold, hundred-fold, five hundred-fold, or one-thousand-fold relative to unmodified bacteria of the same bacterial subtype under the same conditions.

[0270] In one embodiment, the genetically engineered bacteria increase STING agonist production by at least about 80% to 100% relative to unmodified bacteria of the same bacterial subtype under the same conditions, after 4 hours. In one embodiment, the genetically engineered bacteria increase STING agonist production by at least about 90% to 100% relative to unmodified bacteria of the same bacterial subtype under the same conditions after 4 hours. In one specific embodiment, the genetically engineered bacteria increase STING agonist production by at least about 95% to 100% relative to unmodified bacteria of the same bacterial subtype under the same conditions, after 4 hours. In one specific embodiment, the genetically engineered bacteria increase the STING agonist production by at least about 99% to 100% relative to unmodified bacteria of the same bacterial subtype under the same conditions, after 4 hours. In yet another embodiment, the genetically engineered bacteria increase the STING agonist production by at least about 10-50 fold after 4 hours. In yet another embodiment, the genetically engineered bacteria increase STING agonist production by at least about 50-100 fold after 4 hours. In yet another embodiment, the genetically engineered bacteria increase STING agonist production by at least about 100-500 fold after 4 hours. In yet another embodiment, the genetically engineered bacteria increase STING agonist production by at least about 500-1000 fold after 4 hours. In yet another embodiment, the genetically engineered bacteria increase the STING agonist production by at least about 1000-5000 fold after 4 hours. In yet another embodiment, the genetically engineered bacteria increase the STING agonist production by at least about 5000-10000 fold after 4 hours. In yet another embodiment, the genetically engineered bacteria increase STING agonist production by at least about 10000-1000 fold after 4 hours.

[0271] In any of these STING agonist production embodiments, the genetically engineered bacteria are capable of reducing viral infection, e.g., viral infected cell growth and/or proliferation (in vitro during cell culture and/or in vivo) by at least about 0 to 10%, 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, or more as compared to an unmodified bacteria of the same subtype under the same conditions.

[0272] In some embodiments, the genetically engineered bacteria comprising gene sequences encoding dacA (and/or another enzyme for the production of a STING agonists, e.g., cGAS) are able to increase IFN-$1 mRNA or protein levels in macrophages and/or dendritic cells, e.g., in cell culture. In some embodiments, the IFN-.beta.1 mRNA or protein increase dependent on the dose of bacteria administered. In some embodiments, the genetically engineered bacteria comprising gene sequences encoding dacA (and/or another enzyme for the production of a STING agonists, e.g., cGAS) are able to increase IFN-.beta.1 mRNA or protein levels in macrophages and/or dendritic cells. In some embodiments, the IFN-beta1 mRNA or protein increase is dependent on the dosage of bacteria administered.

[0273] In one embodiment, IFN-beta1 mRNA or protein production in target cells is about two-fold, about 3-fold, about 4-fold as compared to levels of IFN-beta1 production observed upon administration of an unmodified bacteria of the same subtype under the same conditions, e.g., at day 2 after first injection of the bacteria. In some embodiments, the genetically engineered bacteria induce the production of at least about 6,000 to 25,000, 15,000 to 25,000, 6,000 to 8,000, 20,000 to 25,000 pg/ml IFN b1 mRNA in bone marrow-derived dendritic cells, e.g., at 4 hours post-stimulation.

[0274] In some embodiments, the genetically engineered bacteria comprising gene sequences encoding dacA (or another enzyme for the production of a STING agonists) can dose-dependently increase IFN-b1 production in bone marrow-derived dendritic cells, e.g., at 2 or 4 hours post stimulation.

[0275] In some embodiments, the genetically engineered bacteria comprising gene sequences encoding dacA (or another enzyme for the production of a STING agonists) are able to reduce viral infection, e.g., at 4 or 9 days after a regimen of 3 bacterial treatments, relative to an unmodified bacteria of the same subtype under the same conditions.

[0276] Strain activity of the STING agonist producing strain can be defined by conducting in vitro measurements c-di-AMP production (in the cell or in the medium). C-di-AMP production can be measured over a time period of 1, 2, 3, 4, 5, 6 hours or greater. In one example, c-di-AMP levels can be measured at 0, 2, or 4 hours. Unmodified Nissle can be used as a baseline in such measurements. If STING agonist producing enzyme is under the control of a promoter which is induced by a chemical inducer, the inducer needs to be added. If STING agonist producing enzyme is under the control of a promoter which is induced by exogenous environmental conditions, such as low-oxygen conditions, the bacterial cells are induced under these conditions, e.g., low oxygen conditions. As an additional baseline measurement, STING agonist producing strains which are inducible can be left uninduced. After the incubation time, levels of c-diAMP can be measured by LC-MS as described herein. In some embodiments, the induced STING agonist producing strain is capable of producing c-di-AMP at a concentration of at least about 0.01 mM to 1.4 mM per 10{circumflex over ( )}9. In some embodiments, the induced STING agonist producing strain is capable of producing c-di-AMP at a concentration of at least about 0.01 mM to 0.02 mM, 0.02 mM to 0.03 mM, 0.03 mM to 0.04 mM, 0.04 mM to 0.05 mM, 0.05 mM to 0.06 mM, 0.06 mM to 0.07 mM, 0.07 mM to 0.08 mM, 0.08 mM to 0.09 mM, 0.09 mM to 0.10 mM, 0.10 mM to 0.12 mM per 10{circumflex over ( )}9 e.g., after 2 or 4 hours. In some embodiments, the induced STING agonist producing strain is capable of producing c-di-AMP at a concentration of at least about 0.1 mM to 0.2 mM, 0.2 mM to 0.3 mM, 0.3 mM to 0.4 mM, 0.4 mM to 0.5 mM, 0.5 mM to 0.6 mM, 0.6 mM to 0.7 mM, 0.7 mM to 0.8 mM, 0.8 mM to 0.9 mM, 0.9 mM to 1 mM, 1 mM to 1.2 mM, 1.2 mM to 1.3 mM, 1.3 mM to 1.4 mM per 10{circumflex over ( )}9 e.g., after 2 or 4 hours.

[0277] Strain activity of the STING agonist producing strain may also be measured using in vitro measurements of activity. In a non-limiting example of an in vitro strain activity measurement, IFN-beta1 induction in RAW 264.7 cells (or other macrophage or dendritic cell) in culture may be measured. Activity of the strain can be measured at various multiplicities of infection (MOI) at various time points. For example, activity can be measured at 1, 2, 3, 4, 5, 6 hours or greater. In one example activity can be measured at 45 minutes or 4 hours. Unmodified Nissle can be used as a baseline in such measurements. If STING agonist producing enzyme is under the control of a promoter which is induced by a chemical inducer, the inducer needs to be added. If STING agonist producing enzyme is under the control of a promoter which is induced by exogenous environmental conditions, such as low-oxygen conditions, the bacterial cells are induced under these conditions, e.g., low oxygen conditions. As an additional baseline measurement, STING agonist producing strains which are inducible can be left uninduced. After the incubation time, IFN-beta levels can be measured from protein extracts or RNA levels can be analyzed, e.g., via PCT based methods. In some embodiments, the induced STING agonist producing strain can elicit a dose-dependent induction of IFN-b levels. In some embodiments, 10{circumflex over ( )}1 to 10{circumflex over ( )}2 (multiplicities of infection (MOI) can induce at least about 20 to 25 times, 25 to 30 times, 30 to 35 times, 35 to 40 times or more greater IFN-beta levels as the unmodified Nissle baseline strain of the same subtype under the same conditions, eg., after 4 hours. In some embodiments, 10{circumflex over ( )}1 to 10{circumflex over ( )}2 (multiplicities of infection (MOI) can induce at least about 10,000 to 12,000, 12,000 to 15,000, 15,000 to 20,000 or 20,000 to 25,000 pg/ml media IFN-beta e.g., after 4 hours.

[0278] In some embodiments, 10{circumflex over ( )}1 to 10{circumflex over ( )}2 (multiplicities of infection (MOI) can induce at least about 10 to 12 times, 12 to 15 times, 15 to 20 times, 20 to 25 times or more greater IFN-beta levels as the wild type Nissle baseline strain of the same subtype under the same conditions, e.g., after 45 minutes. In some embodiments, 10{circumflex over ( )}1 to 10{circumflex over ( )}2 (multiplicities of infection (MOI) can induce at least about 4,000 to 6,000, 6,000 to 8,000, 8,000 to 10,000 or 10,000 to 12,000 pg/ml media IFN-beta e.g., after 45 minutes.

[0279] In some embodiments, the bacteria genetically engineered to produce STING agonists are capable of increasing the response rate by at least about 0 to 10%, 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, 98% or more as compared to an unmodified bacteria of the same subtype under the same conditions. In some embodiments, the genetically engineered bacteria comprising gene sequences encoding dacA, achieve a 100% response rate.

[0280] In some embodiments, the response rate is at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold than observed with than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, the response rate is about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold or more than observed with unmodified bacteria of the same bacterial subtype under the same conditions.

[0281] In some embodiments, the genetically engineered bacteria comprising gene sequences encoding diadenylate cyclases, e.g., DacA, di-GAMP synthases, and/or other STING agonist producing polypeptides increase total T cell numbers in the lymph nodes. In some embodiments, the increase in total T cell numbers in the lymph nodes is at least about 0 to 10%, 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, 98% or more as compared to an unmodified bacteria of the same subtype under the same conditions. In some embodiments, the increase in total T cell numbers is at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold than observed with than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, the increase in total T cell numbers is about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold more than observed with unmodified bacteria of the same bacterial subtype under the same conditions.

[0282] In some embodiments, the genetically engineered bacteria comprising gene sequences encoding diadenylate cyclases, e.g., DacA, di-GAMP synthases, and/or other STING agonist producing polypeptides increase the percentage of activated effector CD4 and CD8 T cells in lymph nodes.

[0283] In some embodiments, the percentage of activated effector CD4 and CD8 T cells in the lymph nodes is at least about 0 to 10%, 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, 98% or more as compared to an unmodified bacteria of the same subtype under the same conditions. In some embodiments, the percentage of activated effector CD4 and CD8 T cells is at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold than observed with than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, the percentage of activated effector CD4 and CD8 T cells is about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold more than observed with unmodified bacteria of the same bacterial subtype under the same conditions. In one embodiment, the gene encoded by the bacteria is DacA and the percentage of activated effector CD4 and CD8 T cells is two to four fold more than observed with unmodified bacteria of the same bacterial subtype under the same conditions.

[0284] In some embodiments, the genetically engineered bacteria comprising gene sequences encoding diadenylate cyclases, e.g., DacA, di-GAMP synthases, and/or other STING agonist producing polypeptides achieve early rise of innate cytokines and a later rise of an effector-T-cell response.

[0285] In some embodiments, the genetically engineered bacteria comprising gene sequences encoding dacA (or other enzymes for production of STING agonists) in the target cells are able to overcome immunological suppression and generating robust innate and adaptive immune responses. In some embodiments, the genetically engineered bacteria comprising gene sequences encoding dacA inhibit proliferation or accumulation of regulatory T cells.

[0286] In some embodiments, the genetically engineered bacteria comprising gene sequences encoding dacA, cGAS, and/or other enzymes for production of STING agonists, achieve early rise of innate cytokines, including but not limited to IL-6, IL-1beta, and MCP-1.

[0287] In some embodiments IL-6 is at least about 0 to 10%, 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, 98% or more induced as compared to an unmodified bacteria of the same subtype under the same conditions. In some embodiments, IL-6 is at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold more induced than observed with than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, the IL-6 is about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold or more induced than observed with unmodified bacteria of the same bacterial subtype under the same conditions. In one embodiment, the gene encoded by the bacteria is dacA and the levels of induced IL-6 is about two to three-fold greater than observed with unmodified bacteria of the same bacterial subtype under the same conditions.

[0288] In some embodiments, the levels of IL-1beta in the target cells is at least about 0 to 10%, 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, 98% or more elevated as compared to an unmodified bacteria of the same subtype under the same conditions. In some embodiments, the levels of IL-1beta are at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold or more elevated than observed with than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, levels of IL-1beta are about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold or more elevated than observed with unmodified bacteria of the same bacterial subtype under the same conditions. In one embodiment, the gene encoded by the bacteria is a diadenylate cyclase, e.g., DacA, a di-GAMP synthase, and/or other STING agonist producing polypeptide and levels of IL-1beta are about 2 fold, 3 fold, or 4 fold more than observed with unmodified bacteria of the same bacterial subtype under the same conditions.

[0289] In some embodiments, the levels of MCP1 in the target cells is at least about 0 to 10%, 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, 98% or more elevated as compared to an unmodified bacteria of the same subtype under the same conditions. In some embodiments, the levels of MCP1 are at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold or more elevated than observed with than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, levels of MCP1 are about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold or more elevated than observed with unmodified bacteria of the same bacterial subtype under the same conditions. In one embodiment, the gene encoded by the bacteria is a diadenylate cyclase, e.g., DacA, a di-GAMP synthase, and/or other STING agonist producing polypeptide and levels of MCP1 are about 2-fold, 3-fold, or 4-fold more than observed with unmodified bacteria of the same bacterial subtype under the same conditions.

[0290] In some embodiments, the genetically engineered bacteria comprising gene sequences encoding diadenylate cyclases, e.g., DacA, di-GAMP synthases, and/or other STING agonist producing polypeptides achieve activation of molecules relevant towards an effector-T-cell response, including but not limited to, Granzyme B, IL-2, and IL-15.

[0291] In some embodiments, the levels of granzyme B in the target cells is at least about 0 to 10%, 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, 98% or more elevated as compared to an unmodified bacteria of the same subtype under the same conditions. In some embodiments, the levels of granzyme B are at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold or more elevated than observed with than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, levels of granzyme B are about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold or more elevated than observed with unmodified bacteria of the same bacterial subtype under the same conditions. In one embodiment, the gene encoded by the bacteria is a diadenylate cyclase, e.g., DacA, a di-GAMP synthase, and/or other STING agonist producing polypeptide and levels of granzyme B are about 2 fold, 3 fold, or 4 fold more than observed with unmodified bacteria of the same bacterial subtype under the same conditions.

[0292] In some embodiments, the levels of IL-2 in the target cells is at least about 0 to 10%, 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, 98% or more elevated as compared to an unmodified bacteria of the same subtype under the same conditions. In some embodiments, the levels of IL-2 are at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold or more elevated than observed with than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, levels of IL-2 are about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold or more elevated than observed with unmodified bacteria of the same bacterial subtype under the same conditions. In one embodiment, the gene encoded by the bacteria is DacA and the levels of IL-2 are about 3 fold, 4 fold, or 5 fold more than observed with unmodified bacteria of the same bacterial subtype under the same conditions.

[0293] In some embodiments, the levels of IL-15 in the target cells is at least about 0 to 10%, 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, 98% or more elevated as compared to an unmodified bacteria of the same subtype under the same conditions. In some embodiments, the levels of IL-15 are at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold or more elevated than observed with than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, levels of IL-15 are at least about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold or more elevated than observed with unmodified bacteria of the same bacterial subtype under the same conditions. In one embodiment, gene encoded by the bacteria is DacA and the levels of IL-15 are about 2-fold, 3-fold, -fold, or 5-fold more than observed with unmodified bacteria of the same bacterial subtype under the same conditions.

[0294] In some embodiments, the levels of IFNg in the target cells is at least about 0 to 10%, 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, 98% or more elevated as compared to an unmodified bacteria of the same subtype under the same conditions. In some embodiments, the levels of IFNg are at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold or more elevated than observed with than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, levels of IFNg are at least about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold or more elevated than observed with unmodified bacteria of the same bacterial subtype under the same conditions. In one embodiment, the gene encoded by the bacteria is a diadenylate cyclase, e.g., DacA, di-GAMP synthase, and/or other STING agonist producing polypeptide and levels of IFNg are about 2 fold, 3 fold, or 4 fold more than observed with unmodified bacteria of the same bacterial subtype under the same conditions.

[0295] In some embodiments, the levels of IL-12 in the target cells is at least about 0 to 10%, 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, 98% or more elevated as compared to an unmodified bacteria of the same subtype under the same conditions. In some embodiments, the levels of IL-12 are at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold or more elevated than observed with than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, levels of IL-12 are at least about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold or more elevated than observed with unmodified bacteria of the same bacterial subtype under the same conditions. In one embodiment, the gene encoded by the bacteria is a diadenylate cyclase, e.g., DacA, a di-GAMP synthase, and/or other STING agonist producing polypeptide and levels of IL-12 are about 2 fold, 3 fold, or 4 fold more than observed with unmodified bacteria of the same bacterial subtype under the same conditions.

[0296] In some embodiments, the levels of TNF-a in the target cells is at least about 0% to 10%, 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, 98% or more elevated as compared to an unmodified bacteria of the same subtype under the same conditions. In some embodiments, the levels of TNF-a are at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold or more elevated than observed with than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, levels of TNF-a are at least about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold or more elevated than observed with unmodified bacteria of the same bacterial subtype under the same conditions. In one embodiment, the gene encoded by the bacteria is a diadenylate cyclase, e.g., DacA, a di-GAMP synthase, and/or other STING agonist producing polypeptide and levels of TNF-a are at least about 2 fold, 3 fold, or 4 fold more than observed with unmodified bacteria of the same bacterial subtype under the same conditions.

[0297] In some embodiments, the levels of GM-CSF in the target cells is at least about 0 to 10%, 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, 98% or more elevated as compared to an unmodified bacteria of the same subtype under the same conditions. In some embodiments, the levels of GM-CSF are at least about 0 to 1.0-fold, 1.0-1.2-fold, 1.2-1.4-fold, 1.4-1.6-fold, 1.6-1.8-fold, 1.8-2-fold, or two-fold or more elevated than observed with than unmodified bacteria of the same bacterial subtype under the same conditions. In yet another embodiment, levels of GM-CSF are about 2 to 3-fold, 3 to 4-fold, 4 to 5-fold, 5 to 6-fold, 6 to 7-fold, 7 to 8-fold, 8 to 9-fold, 9 to 10-fold, 10 to 15-fold, 15 to 20-fold, 20 to 30-fold, 30 to 40-fold, or 40 to 50-fold, 50 to 100-fold, 100 to 500-fold, or 500 to 1000-fold or more elevated than observed with unmodified bacteria of the same bacterial subtype under the same conditions. In one embodiment, the gene encoded by the bacteria is a diadenylate cyclase, e.g., DacA, a di-GAMP synthase, and/or other STING agonist producing polypeptide and levels of GM-CSF are at least about 2 fold, 3 fold, or 4 fold more than observed with unmodified bacteria of the same bacterial subtype under the same conditions.

[0298] In some embodiments, administration of the genetically engineered bacteria comprising gene sequences encoding one or more of a diadenylate cyclase, e.g., DacA, a di-GAMP synthase, and/or other STING agonist producing polypeptide results in long-term immunological memory. In some embodiments, long term immunological memory is established, exemplified by at least about 0 to 10%, 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, 98% or more protection from secondary viral infection challenge compared to naive age-matched controls.

[0299] In some embodiments, the c-di-GAMP synthases, diadenylate cyclases, or other STING agonist producing polypeptides are modified and/or mutated, e.g., to enhance stability, or to increase STING agonism. In some embodiments, c-di-GAMP synthases from Vibrio cholerae or the orthologs thereof (e.g., from Verminephrobacter eiseniae, Kingella denitrificans, and/or Neisseria bacilliformis) or human cGAS is modified and/or mutated, e.g., to enhance stability, or to increase STING agonism. In some embodiments, the diadenylate cyclase from Listeria monocytogenes is modified and/or mutated, e.g., to enhance stability, or to increase STING agonism.

[0300] In some embodiments, the genetically engineered bacteria and/or other microorganisms are capable of producing one or more diadenylate cyclases, c-di-GAMP synthases and/or other STING agonist producing polypeptides under inducing conditions, e.g., under a condition(s) associated with immune suppression. In some embodiments, the genetically engineered bacteria and/or other microorganisms are capable of producing the diadenylate cyclases, c-di-GAMP synthases and/or other STING agonist producing polypeptides in low-oxygen conditions or hypoxic conditions, in the presence of certain molecules or metabolites, in the presence of molecules or metabolites associated with viral infection, or certain tissues, immune suppression, or inflammation, or in the presence of a metabolite that may or may not be present in the gut, circulation, or the target site, and which may be present in vitro during strain culture, expansion, production and/or manufacture such as arabinose, cumate, and salicylate. In some embodiments, the one or more genetically engineered bacteria comprise gene sequence(s) encoding the diadenylate cyclases, c-di-GAMP synthases and/or other STING agonist producing polypeptides, wherein the diadenylate cyclases, c-di-GAMP synthases and/or other STING agonist producing polypeptides are operably linked to a promoter inducible by exogenous environmental conditions of the target cells. In some embodiments, the one or more genetically engineered bacteria comprise gene sequence(s) encoding the diadenylate cyclases, c-di-GAMP synthases and/or other STING agonist producing polypeptides, wherein the diadenylate cyclases, c-di-GAMP synthases and/or other STING agonist producing polypeptides is operably linked to a promoter inducible by cumate or salicylate as described herein. In some embodiments, the gene sequences encoding diadenylate cyclases, c-di-GAMP synthases and/or other STING agonist producing polypeptides are operably linked to a constitutive promoter. In some embodiments, the gene sequences encoding diadenylate cyclases, c-di-GAMP synthases and/or other STING agonist producing polypeptides are present on one or more plasmids (e.g., high copy or low copy) or are integrated into one or more sites in the bacteria and/or other microorganism chromosome(s).

[0301] In any of these embodiments, any of the STING agonist producing strains described herein may comprise an auxotrophic modification. In any of these embodiments, the STING agonist producing strains may comprise an auxotrophic modification in DapA, e.g., a deletion or mutation in DapA. In any of these embodiments, the STING agonist producing strains may further comprise an auxotrophic modification in ThyA e.g., a deletion or mutation in ThyA. In any of these embodiments, the STING agonist producing strains may comprise a DapA and a ThyA auxotrophy. In any of these embodiments, the bacteria may further comprise an endogenous phage modification, e.g., a mutation or deletion, in an endogenous phage. In a non-limiting example the bacterial host is E. coli Nissle and the phage modification comprises a modification in Nissle Phage 3, described herein. In one example, the phage modification is a deletion of one or more genes, e.g., a 10 kb deletion.

[0302] In any of these embodiments describing genetically engineered bacteria comprising gene sequences encoding one or more diadenylate cyclases, c-di-GAMP synthases or other STING agonist producing polypeptides, the genetically engineered bacteria may further comprise gene sequence(s) encoding kynureninase, e.g., kynureninase from Pseudomonas fluorescens and (optionally) having a modification, e.g., mutation or deletion in the TrpE gene. Alternatively the genetically engineered bacteria comprising gene sequences encoding one or more diadenylate cyclases, c-di-GAMP synthases or other STING agonist producing polypeptides may be combined or administered with genetically engineered bacteria comprising gene sequence(s) encoding kynureninase, e.g., kynureninase from Pseudomonas fluorescens and (optionally) having a modification, e.g., mutation or deletion in the TrpE gene.

[0303] In certain embodiments, one or more genetically engineered bacteria comprise gene sequence(s) encoding diadenylate cyclase e.g., DacA, e.g., from Listeria monocytogenes, wherein diadenylate cyclase gene is operably linked to a promoter inducible under exogenous environmental conditions. In one embodiment, the diadenylate cyclase gene is operably linked to a promoter inducible under low oxygen conditions, e.g., a FNR promoter. In certain embodiments, one or more genetically engineered bacteria comprise gene sequence(s) encoding diadenylate cyclase, e.g., dacA, e.g., from Listeria monocytogenes, wherein diadenylate cyclase is operably linked to a promoter inducible by cumate or salicylate as described herein. In certain embodiments, the diadenylate cyclase gene sequences are integrated into the bacterial chromosome. Suitable integration sites are described herein. In a non-limiting example the diadenylate cyclase gene is integrated at HA910. In certain embodiments, the bacteria comprising gene sequences encoding the diadenylate cyclase further comprise an auxotrophic modification. In some embodiments, the modification, e.g., a mutation or deletion is in the dapA gene. In some embodiments, the modification, e.g., a mutation or deletion is in the thyA gene. In some embodiments, the modification, e.g., a mutation or deletion is in both dapA and thyA genes. In any of these embodiments, the bacteria may further comprise a phage modification, e.g., a mutation or deletion in an endogenous prophage. In one example, the prophage modification is a deletion of one or more genes, e.g., a 10 kb deletion. In a non-limiting example, the genetically engineered bacteria comprising gene sequences encoding diadenylate cyclase are derived from E. coli Nissle and the prophage modification comprises a deletion or mutation in Nissle Prophage 3, described herein.

[0304] In certain embodiments genetically engineered bacteria comprising gene sequences encoding one or more diadenylate cyclases, the genetically engineered bacteria may further comprise gene sequence(s) encoding kynureninase, e.g., kynureninase from Pseudomonas fluorescens and (optionally) having a modification, e.g., mutation or deletion in the TrpE gene. Alternatively the genetically engineered bacteria comprising gene sequences encoding one or more diadenylate cyclases may be combined or administered with genetically engineered bacteria comprising gene sequence(s) encoding kynureninase, e.g., kynureninase from Pseudomonas fluorescens and (optionally) having a modification, e.g., mutation or deletion in the TrpE gene.

[0305] In one specific embodiment, one or more genetically engineered bacteria comprise gene sequence(s) encoding diadenylate cyclase e.g., DacA, e.g., from Listeria monocytogenes, wherein the diadenylate cyclase gene is operably linked to a promoter inducible under low oxygen conditions, e.g., a FNR promoter. The dacA gene sequences are integrated into the bacterial chromosome, e.g., at integration site HA910. The bacteria further comprise a auxotrophic modification, e.g., a mutation or deletion in dapA or thyA or both genes. The bacteria may further comprise an endogenous phage modification, e.g., a mutation or deletion, in an endogenous phage, e.g., a 10 kb deletion. In one specific embodiment, the genetically engineered bacteria are derived from E. coli Nissle and the phage modification comprises a deletion or mutation in Nissle Phage 3, e.g., as described herein.

[0306] In another specific embodiment, the genetically engineered bacteria may further comprise gene sequence(s) encoding kynureninase, e.g., kynureninase from Pseudomonas fluorescens and (optionally) having a modification, e.g., mutation or deletion in the TrpE gene. Alternatively the genetically engineered bacteria may be combined or administered with genetically engineered bacteria comprising gene sequence(s) encoding kynureninase, e.g., kynureninase from Pseudomonas fluorescens and (optionally) having a modification, e.g., mutation or deletion in the TrpE gene.

[0307] In certain embodiments, one or more genetically engineered bacteria comprise gene sequence(s) encoding cGAMP synthase e.g., human cGAS, wherein the cGAS gene is operably linked to a promoter inducible under exogenous environmental conditions. In one embodiment, the cGAS gene is operably linked to a promoter inducible under low oxygen conditions, e.g., a FNR promoter. In certain embodiments, one or more genetically engineered bacteria comprise gene sequence(s) encoding cGAS, e.g., human cGAS, wherein the cGAS gene is operably linked to a promoter inducible by cumate or salicylate as described herein. In certain embodiments, the cGAS gene sequences are integrated into the bacterial chromosome. Suitable integration sites are described herein and known in the art. In certain embodiments, the bacteria comprising gene sequences encoding cGAS further comprise an auxotrophic modification, e.g., a mutation or deletion in dapA or thyA or both genes. In some embodiments, the modification, e.g., a mutation or deletion is in the dapA gene. In some embodiments, the modification, e.g., a mutation or deletion is in thyA gene. In some embodiments, the modification, e.g., a mutation or deletion is in both dapA and thyA genes. In any of these embodiments, the bacteria may further comprise a prophage modification, e.g., a mutation or deletion, in an endogenous prophage. In one example, the prophage modification is a deletion of one or more genes, e.g., a 10 kb deletion. In a non-limiting example, the genetically engineered bacteria comprising gene sequences encoding cGAS are derived from E. coli Nissle and the prophage modification comprises a deletion or mutation in Nissle Phage 3, described herein.

[0308] In any of these embodiments describing genetically engineered bacteria comprising gene sequences encoding one or more cGAS, the genetically engineered bacteria may further comprise gene sequence(s) encoding kynureninase, e.g., kynureninase from Pseudomonas fluorescens and (optionally) having a modification, e.g., mutation or deletion in the TrpE gene. Alternatively the genetically engineered bacteria comprising gene sequences encoding one or more cGAS may be combined or administered with genetically engineered bacteria comprising gene sequence(s) encoding kynureninase, e.g., kynureninase from Pseudomonas fluorescens and (optionally) having a modification, e.g., mutation or deletion in the TrpE gene.

[0309] In one embodiment, one or more genetically engineered bacteria comprise gene sequence(s) encoding cGAS e.g., human cGAS, wherein the cGAS gene is operably linked to a promoter inducible under low oxygen conditions, e.g., an FNR promoter. The cGAS gene sequences are integrated into the bacterial chromosome. The bacteria further comprise an auxotrophic modification, e.g., a mutation or deletion in dapA or thyA or both genes. The bacteria may further comprise an endogenous phage modification, e.g., a mutation or deletion, in an endogenous phage, e.g., a 10 kb deletion. In one specific embodiment, the genetically engineered bacteria are derived from E. coli Nissle and the phage modification comprises a deletion or mutation in Nissle Phage 3, e.g., as described herein.

[0310] In another specific embodiment, the genetically engineered bacteria comprising gene sequences encoding one or more cGAS, the genetically engineered bacteria may further comprise gene sequence(s) encoding kynureninase, e.g., kynureninase from Pseudomonas fluorescens and (optionally) having a modification, e.g., mutation or deletion in the TrpE gene. Alternatively the genetically engineered bacteria comprising gene sequences encoding one or more cGAS may be combined or administered with genetically engineered bacteria comprising gene sequence(s) encoding kynureninase, e.g., kynureninase from Pseudomonas fluorescens and (optionally) having a modification, e.g., mutation or deletion in the TrpE gene.

[0311] In certain embodiments, one or more genetically engineered bacteria comprise gene sequence(s) encoding diadenylate cyclase e.g., DacA, e.g., from Listeria monocytogenes, and cGAMP synthase e.g., human cGAS. In certain embodiments, the diadenylate cyclase gene and/or the cGAS gene are operably linked to a promoter inducible under exogenous environmental conditions. In certain embodiments, the diadenylate cyclase gene and/or cGAS gene are operably linked to a promoter inducible by cumate or salicylate, or another chemical inducer. In certain embodiments, the diadenylate cyclase gene and/or cGAS gene are operably linked to a constitutive promoter. In one embodiment, the diadenylate cyclase gene and/or cGAS gene is operably linked to a promoter inducible under low oxygen conditions, e.g., an FNR promoter. In certain embodiments, one or more genetically engineered bacteria comprise gene sequence(s) encoding diadenylate cyclase gene, e.g., dacA, e.g., from Listeria monocytogenes, and cGAS, e.g., human cGAS, wherein the diadenylate cyclase gene and/or cGAS gene is operably linked to a promoter inducible by cumate or salicylate as described herein. In certain embodiments, the diadenylate cyclase and cGAS gene sequences are integrated into the bacterial chromosome. Suitable integration sites are described herein and known in the art. In certain embodiments, the bacteria comprising gene sequences encoding diadenylate cyclase and cGAS further comprise a mutation or deletion in dapA or thyA or both genes. In any of these embodiments, the bacteria may further comprise a prophage modification, e.g., a mutation or deletion, in an endogenous prophage. In one example, the prophage modification is a deletion of one or more genes, e.g., a 10 kb deletion. In a non-limiting example, the genetically engineered bacteria comprising gene sequences encoding diadenylate cyclase and cGAS are derived from E. coli Nissle and the prophage modification comprises a deletion or mutation in Nissle Phage 3, described herein.

[0312] In any of these embodiments describing genetically engineered bacteria comprising gene sequences encoding one or more diadenylate cyclases and cGAS producing polypeptides, the genetically engineered bacteria may further comprise gene sequence(s) encoding kynureninase, e.g., kynureninase from Pseudomonas fluorescens and (optionally) having a modification, e.g., mutation or deletion in the TrpE gene. Alternatively the genetically engineered bacteria comprising gene sequences encoding one or more diadenylate cyclases and cGAS polypeptides may be combined or administered with genetically engineered bacteria comprising gene sequence(s) encoding kynureninase, e.g., kynureninase from Pseudomonas fluorescens and (optionally) having a modification, e.g., mutation or deletion in the TrpE gene.

[0313] In one specific embodiment, one or more genetically engineered bacteria comprise gene sequence(s) encoding diadenylate cyclase e.g., DacA, e.g., from Listeria monocytogenes, and cGAS e.g., human cGAS, wherein the diadenylate cyclase gene and/or cGAS gene is operably linked to a promoter inducible under low oxygen conditions, e.g., an FNR promoter. The diadenylate cyclase gene and cGAS gene sequences are integrated into the bacterial chromosome. The bacteria further comprise an auxotrophic modification, e.g., a mutation or deletion in dapA or thyA or both genes. The bacteria may further comprise an endogenous phage modification, e.g., a mutation or deletion, in an endogenous phage, e.g., a 10 kb deletion. In one specific embodiment, the genetically engineered bacteria are derived from E. coli Nissle and the phage modification comprises a deletion or mutation in Nissle Phage 3, e.g., as described herein.

[0314] In another specific embodiment, the genetically engineered bacteria comprising gene sequences encoding one or more diadenylate cyclases and cGAS polypeptides, the genetically engineered bacteria may further comprise gene sequence(s) encoding kynureninase, e.g., kynureninase from Pseudomonas fluorescens and (optionally) having a modification, e.g., mutation or deletion in the TrpE gene. Alternatively, the genetically engineered bacteria comprising gene sequences encoding one or more diadenylate cyclases and cGAS polypeptides may be combined or administered with genetically engineered bacteria comprising gene sequence(s) encoding kynureninase, e.g., kynureninase from Pseudomonas fluorescens and (optionally) having a modification, e.g., mutation or deletion in the TrpE gene.

[0315] In any of these embodiments, the one or more bacteria genetically engineered to produce one or more STING agonists may be administered alone or in combination with one or more immune checkpoint inhibitors described herein, including but not limited to anti-CTLA4, anti-PD1, or anti-PD-L1 antibodies. In some embodiments, the one or more genetically engineered bacteria which produce STING agonists evoke immunological memory when administered in combination with checkpoint inhibitor therapy.

[0316] In any of these embodiments, the one or more bacteria genetically engineered to produce STING agonists may be genetically engineered to produce and secrete or display on their surface one or more immune checkpoint inhibitors described herein, including but not limited to anti-CTLA4, anti-PD1, or anti-PD-L1 antibodies. In some embodiments, the one or more genetically engineered bacteria which comprise gene sequences encoding one or more enzymes for STING agonist production and gene sequences encoding one or more immune checkpoint inhibitor antibodies, e.g., scFv antibodies, promote immunological memory upon rechallenge/reoccurrence of a viral infection.

[0317] In any of these embodiments, the one or more bacteria genetically engineered to produce one or more STING agonists may be administered alone or in combination with one or more immune stimulatory agonists described herein, e.g., agonistic antibodies, including but not limited to anti-OX40, anti-41BB, or anti-GITR antibodies. In some embodiments, the one or more genetically engineered bacteria which produce STING agonists evoke immunological memory when administered in combination with anti-OX40, anti-41BB, or anti-GITR antibodies.

[0318] In any of these embodiments, the one or more bacteria genetically engineered to produce STING agonists may be genetically engineered to produce and secrete or display on their surface one or more immune stimulatory agonists described herein, e.g., agonistic antibodies, including but not limited to anti-OX40, anti-41BB, or anti-GITR antibodies. In some embodiments, the one or more genetically engineered bacteria comprising gene sequences encoding one or more STING agonist producing enzymes and gene sequences encoding one or more costimulatory antibodies, e.g., selected from anti-OX40, anti-41BB, or anti-GITR antibodies evoke immunological memory.

[0319] Also, in some embodiments, the genetically engineered bacteria and/or other microorganisms are further capable of expressing any one or more of the described circuits and further comprise one or more of the following: (1) one or more auxotrophies, such as any auxotrophies known in the art and provided herein, e.g., dapA and thyA auxotrophy, (2) one or more kill switch circuits, such as any of the kill-switches described herein or otherwise known in the art, (3) one or more antibiotic resistance circuits, (4) one or more transporters for importing biological molecules or substrates, such any of the transporters described herein or otherwise known in the art, (5) one or more secretion circuits, such as any of the secretion circuits described herein and otherwise known in the art, (6) one or more surface display circuits, such as any of the surface display circuits described herein and otherwise known in the art (7) one or more circuits for the production or degradation of one or more metabolites (e.g., kynurenine, tryptophan, adenosine, arginine) described herein, (8) one or more immune initiators (e.g. STING agonist, CD40L, SIRP.alpha.) described herein, (9) one or more immune sustainers (e.g. IL-15, IL-12, CXCL10) described herein, and (10) combinations of one or more of such additional circuits.

Regulating Expression

[0320] In some embodiments, the bacterial cell comprises a stably maintained plasmid or chromosome carrying the gene(s) encoding payload (s), such that the payload(s) can be expressed in the host cell, and the host cell is capable of survival and/or growth in vitro, e.g., in medium, and/or in vivo. In some embodiments, bacterial cell comprises two or more distinct payloads or operons, e.g., two or more payload genes. In some embodiments, bacterial cell comprises three or more distinct transporters or operons, e.g., three or more payload genes. In some embodiments, bacterial cell comprises 4, 5, 6, 7, 8, 9, 10, or more distinct payloads or operons, e.g., 4, 5, 6, 7, 8, 9, 10, or more payload genes.

[0321] Herein the terms "payload" "polypeptide of interest" or "polypeptides of interest", "protein of interest", "proteins of interest", "payloads" "effector molecule", "effector" refers to one or more effector molecules described herein and/or one or more enzyme(s) or polypeptide(s) function as enzymes needed for the production of such effector molecules. Non-limiting examples of payloads include a viral COVID19 protein, a STING agonist, etc.

[0322] As used herein, the term "polypeptide of interest" or "polypeptides of interest", "protein of interest", "proteins of interest", "payload", "payloads" further includes any or a plurality of any of the viral proteins, STING agonists, tryptophan synthesis enzymes, kynurenine degrading enzymes, adenosine degrading enzymes, arginine producing enzymes, and other metabolic pathway enzymes described herein. As used herein, the term "gene of interest" or "gene sequence of interest" includes any or a plurality of any of the gene(s) an/or gene sequence(s) and or gene cassette(s) encoding one or more immune modulator(s) described herein.

[0323] In some embodiments, the genetically engineered bacteria comprise multiple copies of the same payload gene(s). In some embodiments, the gene encoding the payload is present on a plasmid and operably linked to a directly or indirectly inducible promoter. In some embodiments, the gene encoding the payload is present on a plasmid and operably linked to a constitutive promoter. In some embodiments, the gene encoding the payload is present on a plasmid and operably linked to a promoter that is induced under low-oxygen or anaerobic conditions. In some embodiments, the gene encoding the payload is present on plasmid and operably linked to a promoter that is induced by exposure to tetracycline or arabinose, cumate, and salicylate, or another chemical or nutritional inducer described herein.

[0324] In some embodiments, the gene encoding the payload is present on a chromosome and operably linked to a directly or indirectly inducible promoter. In some embodiments, the gene encoding the payload is present on a chromosome and operably linked to a constitutive promoter. In some embodiments, the gene encoding the payload is present in the chromosome and operably linked to a promoter that is induced under low-oxygen or anaerobic conditions. In some embodiments, the gene encoding the payload is present on chromosome and operably linked to a promoter that is induced by exposure to tetracycline or arabinose, cumate, and salicylate, or another chemical or nutritional inducer described herein.

[0325] In some embodiments, the genetically engineered bacteria comprise two or more payloads, all of which are present on the chromosome. In some embodiments, the genetically engineered bacteria comprise two or more payloads, all of which are present on one or more same or different plasmids. In some embodiments, the genetically engineered bacteria comprise two or more payloads, some of which are present on the chromosome and some of which are present on one or more same or different plasmids.

[0326] In any of the embodiments described above, the one or more payload(s) for producing the effector or immune modulator combinations are operably linked to one or more directly or indirectly inducible promoter(s). In some embodiments, the one or more payload(s) are operably linked to a directly or indirectly inducible promoter that is induced under exogeneous environmental conditions, e.g., conditions found in tissue specific conditions. In some embodiments, the one or more payload(s) are operably linked to a directly or indirectly inducible promoter that is induced by metabolites found in the tissue specific conditions. In some embodiments, the one or more payload(s) are operably linked to a directly or indirectly inducible promoter that is induced under low-oxygen or anaerobic conditions. In some embodiments, the one or more payload(s) are operably linked to a directly or indirectly inducible promoter that is induced under inflammatory conditions (e.g., RNS, ROS), as described herein. In some embodiments, the one or more payload(s) are operably linked to a directly or indirectly inducible promoter that is induced under immunosuppressive conditions, e.g., as found in the target site, as described herein. In some embodiments, the two or more gene sequence(s) are linked to a directly or indirectly inducible promoter that is induced by exposure a chemical or nutritional inducer, which may or may not be present under in vivo conditions and which may be present during in vitro conditions (such as strain culture, expansion, manufacture), such as tetracycline or arabinose, cumate, and salicylate, or others described herein. In some embodiments, the two or more payloads are all linked to a constitutive promoter.

[0327] In some embodiments, the promoter is induced under in vivo conditions, e.g., the gut, as described herein. In some embodiments, the promoters is induced under in vitro conditions, e.g., various cell culture and/or cell manufacturing conditions, as described herein. In some embodiments, the promoter is induced under in vivo conditions, e.g., the gut, as described herein, and under in vitro conditions, e.g., various cell culture and/or cell production and/or manufacturing conditions, as described herein.

[0328] In some embodiments, the promoter that is operably linked to the gene encoding the payload is directly induced by exogenous environmental conditions (e.g., in vivo and/or in vitro and/or production/manufacturing conditions). In some embodiments, the promoter that is operably linked to the gene encoding the payload is indirectly induced by exogenous environmental conditions (e.g., in vivo and/or in vitro and/or production/manufacturing conditions).

FNR Dependent Regulation

[0329] The genetically engineered bacteria of the invention comprise a gene or gene cassette for producing an immune modulator, wherein the gene or gene cassette is operably linked to a directly or indirectly inducible promoter that is controlled by exogenous environmental condition(s). In some embodiments, the inducible promoter is an oxygen level-dependent promoter and an immune modulator is expressed in low-oxygen, microaerobic, or anaerobic conditions. For example, in low oxygen conditions, the oxygen level-dependent promoter is activated by a corresponding oxygen level-sensing transcription factor, thereby driving production of an immune modulator.

[0330] Bacteria have evolved transcription factors that are capable of sensing oxygen levels. Different signaling pathways may be triggered by different oxygen levels and occur with different kinetics. An oxygen level-dependent promoter is a nucleic acid sequence to which one or more oxygen level-sensing transcription factors is capable of binding, wherein the binding and/or activation of the corresponding transcription factor activates downstream gene expression. In one embodiment, the genetically engineered bacteria comprise a gene or gene cassette for producing a payload under the control of an oxygen level-dependent promoter. In a more specific aspect, the genetically engineered bacteria comprise a gene or gene cassette for producing a payload under the control of an oxygen level-dependent promoter that is activated under low-oxygen or anaerobic environments.

[0331] In certain embodiments, the bacterial cell comprises a gene encoding a payload which is operably linked to a fumarate and nitrate reductase regulator (FNR) responsive promoter. In certain embodiments, the bacterial cell comprises a gene encoding a payload expressed under the control of a fumarate and nitrate reductase regulator (FNR) responsive promoter. In E. coli, FNR is a major transcriptional activator that controls the switch from aerobic to anaerobic metabolism (Unden et al., 1997). In the anaerobic state, FNR dimerizes into an active DNA binding protein that activates hundreds of genes responsible for adapting to anaerobic growth. In the aerobic state, FNR is prevented from dimerizing by oxygen and is inactive. FNR responsive promoters include, but are not limited to, the FNR responsive promoters of SEQ ID NO: 563-579. Underlined sequences are predicted ribosome binding sites, and bolded sequences are restriction sites used for cloning.

[0332] FNR promoter sequences are known in the art, and any suitable FNR promoter sequence(s) may be used in the genetically engineered bacteria of the invention. Any suitable FNR promoter(s) may be combined with any suitable payload.

[0333] As used herein the term "payload" refers to one or more effector molecules, e.g. immune modulator(s), including but not limited to immune initiators and immune sustainers described herein.

[0334] Non-limiting FNR promoter sequences are provided in SEQ ID NO: 563-579. In some embodiments, the genetically engineered bacteria of the disclosure comprise a payload, e.g., an effector or an immune modulator, which is operably linked to a low oxygen inducible, e.g., FNR regulated promoter comprising: SEQ ID NO: 563, SEQ ID NO: 564, SEQ ID NO: 565, SEQ ID NO: 566, SEQ ID NO: 567, SEQ ID NO: 568, SEQ ID NO: 569, nirB1 promoter (SEQ ID NO: 570), nirB2 promoter (SEQ ID NO: 571), nirB3 promoter (SEQ ID NO: 572), ydfZ promoter (SEQ ID NO: 573), nirB promoter fused to a strong ribosome binding site (SEQ ID NO: 574), ydfZ promoter fused to a strong ribosome binding site (SEQ ID NO: 575), fnrS, an anaerobically induced small RNA gene (fnrS1 promoter SEQ ID NO: 576 or fnrS2 promoter SEQ ID NO: 577), nirB promoter fused to a crp binding site (SEQ ID NO: 578), and fnrS fused to a crp binding site (SEQ ID NO: 579). In some embodiments, the FNR-responsive promoter is at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% homologous to a sequence selected from SEQ ID NOs: 563-579. In another embodiment, the genetically engineered bacteria comprise a gene sequence comprising an FNR-responsive promoter comprising a sequence selected from SEQ ID NOs: 563-579. In yet another embodiment, the FNR-responsive promoter consists of a sequence selected from SEQ ID NOs: 563-579.

[0335] In some embodiments, the genetically engineered bacteria of the disclosure comprise a gene encoding an effector molecule, e.g., an immune initiator or immune stimulator, which is operably linked to an FNR-responsive promoter which is at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% homologous to a sequence selected from SEQ ID NOs: 1281 or SEQ ID NO: 1282. In another embodiment, the genetically engineered bacteria comprise encode an effector molecule operably linked to an FNR-responsive promoter comprising a sequence selected from SEQ ID NOs: 1281 or SEQ ID NO: 1282. In yet another embodiment, the FNR-responsive promoter consists of a sequence selected from SEQ ID NOs: 1281 or SEQ ID NO: 1282.

[0336] In some embodiments, multiple distinct FNR nucleic acid sequences are inserted in the genetically engineered bacteria. In alternate embodiments, the genetically engineered bacteria comprise a gene encoding a payload expressed under the control of an alternate oxygen level-dependent promoter, e.g., DNR (Trunk et al., 2010) or ANR (Ray et al., 1997). In these embodiments, expression of the payload gene is particularly activated in a low-oxygen or anaerobic environment, such as in the gut. In some embodiments, gene expression is further optimized by methods known in the art, e.g., by optimizing ribosomal binding sites and/or increasing mRNA stability. In one embodiment, the mammalian gut is a human mammalian gut.

[0337] In another embodiment, the genetically engineered bacteria comprise the gene or gene cassette for producing an immune modulator expressed under the control of anaerobic regulation of arginine deiminase and nitrate reduction transcriptional regulator (ANR). In P. aeruginosa, ANR is "required for the expression of physiological functions which are inducible under oxygen-limiting or anaerobic conditions" (Winteler et al., 1996; Sawers 1991). P. aeruginosa ANR is homologous with E. coli FNR, and "the consensus FNR site (TTGAT----ATCAA) was recognized efficiently by ANR and FNR" (Winteler et al., 1996). Like FNR, in the anaerobic state, ANR activates numerous genes responsible for adapting to anaerobic growth. In the aerobic state, ANR is inactive. Pseudomonas fluorescens, Pseudomonas putida, Pseudomonas syringae, and Pseudomonas mendocina all have functional analogs of ANR (Zimmermann et al., 1991). Promoters that are regulated by ANR are known in the art, e.g., the promoter of the arcDABC operon (see, e.g., Hasegawa et al., 1998).

[0338] In other embodiments, the one or more gene sequence(s) for producing a payload are expressed under the control of an oxygen level-dependent promoter fused to a binding site for a transcriptional activator, e.g., CRP. CRP (cyclic AMP receptor protein or catabolite activator protein or CAP) plays a major regulatory role in bacteria by repressing genes responsible for the uptake, metabolism, and assimilation of less favorable carbon sources when rapidly metabolizable carbohydrates, such as glucose, are present (Wu et al., 2015). This preference for glucose has been termed glucose repression, as well as carbon catabolite repression (Deutscher, 2008; Gorke and Stulke, 2008). In some embodiments, the gene or gene cassette for producing an immune modulator is controlled by an oxygen level-dependent promoter fused to a CRP binding site. In some embodiments, the one or more gene sequence(s) for a payload are controlled by a FNR promoter fused to a CRP binding site. In these embodiments, cyclic AMP binds to CRP when no glucose is present in the environment. This binding causes a conformational change in CRP, and allows CRP to bind tightly to its binding site. CRP binding then activates transcription of the gene or gene cassette by recruiting RNA polymerase to the FNR promoter via direct protein-protein interactions. In the presence of glucose, cyclic AMP does not bind to CRP and transcription of the gene or gene cassette for producing a payload is repressed. In some embodiments, an oxygen level-dependent promoter (e.g., an FNR promoter) fused to a binding site for a transcriptional activator is used to ensure that the gene or gene cassette for producing a payload is not expressed under anaerobic conditions when sufficient amounts of glucose are present, e.g., by adding glucose to growth media in vitro.

[0339] In some embodiments, the genetically engineered bacteria comprise an oxygen level-dependent promoter from a different species, strain, or substrain of bacteria. In some embodiments, the genetically engineered bacteria comprise an oxygen level-sensing transcription factor, e.g., FNR, ANR or DNR, from a different species, strain, or substrain of bacteria. In some embodiments, the genetically engineered bacteria comprise an oxygen level-sensing transcription factor and corresponding promoter from a different species, strain, or substrain of bacteria. The heterologous oxygen-level dependent transcriptional regulator and/or promoter increases the transcription of genes operably linked to said promoter, e.g., one or more gene sequence(s) for producing the payload(s) in a low-oxygen or anaerobic environment, as compared to the native gene(s) and promoter in the bacteria under the same conditions. In certain embodiments, the non-native oxygen-level dependent transcriptional regulator is an FNR protein from N. gonorrhoeae (see, e.g., Isabella et al., 2011). In some embodiments, the corresponding wild-type transcriptional regulator is left intact and retains wild-type activity. In alternate embodiments, the corresponding wild-type transcriptional regulator is deleted or mutated to reduce or eliminate wild-type activity.

[0340] In some embodiments, the genetically engineered bacteria comprise a wild-type oxygen-level dependent transcriptional regulator, e.g., FNR, ANR, or DNR, and corresponding promoter that is mutated relative to the wild-type promoter from bacteria of the same subtype. The mutated promoter enhances binding to the wild-type transcriptional regulator and increases the transcription of genes operably linked to said promoter, e.g., the gene encoding the payload, in a low-oxygen or anaerobic environment, as compared to the wild-type promoter under the same conditions. In some embodiments, the genetically engineered bacteria comprise a wild-type oxygen-level dependent promoter, e.g., FNR, ANR, or DNR promoter, and corresponding transcriptional regulator that is mutated relative to the wild-type transcriptional regulator from bacteria of the same subtype. The mutated transcriptional regulator enhances binding to the wild-type promoter and increases the transcription of genes operably linked to said promoter, e.g., the gene encoding the payload, in a low-oxygen or anaerobic environment, as compared to the wild-type transcriptional regulator under the same conditions. In certain embodiments, the mutant oxygen-level dependent transcriptional regulator is an FNR protein comprising amino acid substitutions that enhance dimerization and FNR activity (see, e.g., Moore et al., (2006). In some embodiments, both the oxygen level-sensing transcriptional regulator and corresponding promoter are mutated relative to the wild-type sequences from bacteria of the same subtype in order to increase expression of the payload in low-oxygen conditions.

[0341] In some embodiments, the bacterial cells comprise multiple copies of the endogenous gene encoding the oxygen level-sensing transcriptional regulator, e.g., the FNR gene. In some embodiments, the gene encoding the oxygen level-sensing transcriptional regulator is present on a plasmid. In some embodiments, the gene encoding the oxygen level-sensing transcriptional regulator and the gene encoding the payload are present on different plasmids. In some embodiments, the gene encoding the oxygen level-sensing transcriptional regulator and the gene encoding the payload are present on the same plasmid.

[0342] In some embodiments, the gene encoding the oxygen level-sensing transcriptional regulator is present on a chromosome. In some embodiments, the gene encoding the oxygen level-sensing transcriptional regulator and the gene encoding the payload are present on different chromosomes. In some embodiments, the gene encoding the oxygen level-sensing transcriptional regulator and the gene encoding the payload are present on the same chromosome. In some instances, it may be advantageous to express the oxygen level-sensing transcriptional regulator under the control of an inducible promoter in order to enhance expression stability. In some embodiments, expression of the transcriptional regulator is controlled by a different promoter than the promoter that controls expression of the gene encoding the payload. In some embodiments, expression of the transcriptional regulator is controlled by the same promoter that controls expression of the payload. In some embodiments, the transcriptional regulator and the payload are divergently transcribed from a promoter region.

RNS-Dependent Regulation

[0343] In some embodiments, the genetically engineered bacterium that expresses a payload under the control of a promoter that is activated by inflammatory conditions. In one embodiment, the gene for producing the payload is expressed under the control of an inflammatory-dependent promoter that is activated in inflammatory environments, e.g., a reactive nitrogen species or RNS promoter. In some embodiments, the genetically engineered bacteria of the invention comprise a tunable regulatory region that is directly or indirectly controlled by a transcription factor that is capable of sensing at least one reactive nitrogen species. Suitable RNS inducible promoters, e.g., inducible by reactive nitrogen species are described in International Patent Application PCT/US2017/013072, filed Jan. 11, 2017, published as WO2017/123675, the contents of which is herein incorporated by reference in its entirety.

[0344] Examples of transcription factors that sense RNS and their corresponding RNS-responsive genes, promoters, and/or regulatory regions include, but are not limited to, those shown in Table 3.

TABLE-US-00003 TABLE 3 Examples of RNS-sensing transcription factors and RNS-responsive genes RNS-sensing Primarily Examples of responsive transcription capable genes, promoters, factor: of sensing: and/or regulatory regions: NsrR NO norB, aniA, nsrR, hmpA, ytfE, ygbA, hcp, hcr, nrfA, aox NorR NO norVW, nor DNR NO norCB, nir, nor, nos

ROS-Dependent Regulation

[0345] In some embodiments, the genetically engineered bacterium that expresses a payload under the control of a promoter that is activated by conditions of cellular damage. In one embodiment, the gene for producing the payload is expressed under the control of a cellular damaged-dependent promoter that is activated in environments in which there is cellular or tissue damage, e.g., a reactive oxygen species or ROS promoter. In some embodiments, the genetically engineered bacteria of the invention comprise a tunable regulatory region that is directly or indirectly controlled by a transcription factor that is capable of sensing at least one reactive oxygen species. Suitable ROS inducible promoters, e.g., inducible by reactive oxygen species are described in International Patent Application PCT/US2017/013072, filed Jan. 11, 2017, published as WO2017/123675, the contents of which is herein incorporated by reference in its entirety.

[0346] Examples of transcription factors that sense ROS and their corresponding ROS-responsive genes, promoters, and/or regulatory regions include, but are not limited to, those shown in Table 4.

TABLE-US-00004 TABLE 4 Examples of ROS-sensing transcription factors and ROS-responsive genes ROS-sensing Primarily capable of Examples of responsive genes, transcription factor: sensing: promoters, and/or regulatory regions: OxyR H.sub.2O.sub.2 ahpC; ahpF; dps; dsbG; fhuF; flu; fur; gor; grxA; hemH; katG; oxyS; sufA; suf73; sufC; sufD; sufE; sufS; trxC; uxuA; yaaA; yaeH; yaiA; ybjM; ydcH; ydeN; ygaQ; yljA; ytfK PerR H.sub.2O.sub.2 katA; ahpCF; mrgA; zoaA; fur; hemAXCDBL; srfA OhrR Organic peroxides NaOCl ohrA SoxR .cndot.O.sub.2.sup.- soxS NO.cndot. (also capable of sensing H.sub.2O.sub.2) RosR H.sub.2O.sub.2 rbtT; tnp16a; rluC1; tnp5a; mscL; tnp2d; phoD; tnp15b; pstA; tnp5b; xylC; gabD1; rluC2; cgtS9; azlC; narKGHJI; rosR

Other Promoters

[0347] In some embodiments, the genetically engineered bacteria comprise the gene or gene cassette for producing an immune modulator expressed under the control of an inducible promoter that is responsive to specific molecules or metabolites in the environment, e.g., a specific tissue, or the mammalian gut. Any molecule or metabolite found in the mammalian gut, in a healthy and/or disease state, may be used to induce payload expression.

[0348] In alternate embodiments, the gene or gene cassette for producing an immune modulator is operably linked to a nutritional or chemical inducer which is not present in the environment, e.g., a specific tissue, or the mammalian gut. In some embodiments, the nutritional or chemical inducer is administered prior, concurrently or sequentially with the genetically engineered bacteria.

Other Inducible Promoters

[0349] In some embodiments, one or more gene sequence(s) encoding polypeptides of interest described herein is present on a plasmid and operably linked to promoter a directly or indirectly inducible by one or more nutritional and/or chemical inducer(s) and/or metabolite(s). In some embodiments, the bacterial cell comprises a stably maintained plasmid or chromosome carrying the gene encoding the immune modulator, which is induced by one or more nutritional and/or chemical inducer(s) and/or metabolite(s), such that the immune modulator can be expressed in the host cell, and the host cell is capable of survival and/or growth in vitro, e.g., under culture conditions, and/or in vivo, e.g., in the gut.

[0350] In some embodiments, expression of one or more displayed proteins (e.g., viral, bacterial, fungal, and cancer protein) and or one or more immune modulator(s) and/or other polypeptide(s) of interest is driven directly or indirectly by one or more arabinose, cumate, and salicylate inducible promoter(s) in vivo. In some embodiments, the promoter is directly or indirectly induced by a chemical and/or nutritional inducer and/or metabolite which is co-administered with the genetically engineered bacteria of the invention. In some embodiments, inducers are administered intranasally at a defined time before bacterial injection into the target site. In some embodiments, inducers are administered intranasally at a defined time after bacterial injection into the target site. In some embodiments, inducers are administered intranasally concurrently with bacterial injection into the target site. In some embodiments, inducers are administered intravenously at a defined time before bacterial injection into the target site. In some embodiments, inducers are administered intravenously at a defined time after bacterial injection into the target site. In some embodiments, inducers are administered intravenously concurrently with bacterial injection into the target site. In some embodiments, inducers are administered subcutaneously at a defined time before bacterial injection into the target site. In some embodiments, inducers are administered subcutaneously at a defined time after bacterial injection into the target site. In some embodiments, inducers are administered subcutaneously concurrently with bacterial injection into the target site.

[0351] In some embodiments, inducers are administered intranasally at a defined time before bacterial injection into the target site. In some embodiments, inducers are administered intranasally at a defined time after bacterial injection into the target site. In some embodiments, inducers are administered intranasally concurrently with bacterial injection into the target site. In some embodiments, inducers are administered intravenously at a defined time before bacterial injection into the target site. In some embodiments, inducers are administered intravenously at a defined time after bacterial injection into the target site. In some embodiments, inducers are administered intravenously concurrently with intravenous bacterial administration. In some embodiments, inducers are administered subcutaneously at a defined time before bacterial injection into the target site. In some embodiments, inducers are administered subcutaneously at a defined time after bacterial injection into the target site. In some embodiments, inducers are administered subcutaneously concurrently with intravenous bacterial administration.

[0352] In some embodiments, expression of one or more display proteins comprising a displayed protein (e.g., viral, bacterial, fungal, and cancer protein) and/or one or more immune modulator(s) and/or other polypeptide(s) of interest, is driven directly or indirectly by one or more promoter(s) induced by a chemical and/or nutritional inducer and/or metabolite during in vitro growth, preparation, or manufacturing of the strain prior to in vivo administration. In some embodiments, the promoter(s) induced by a chemical and/or nutritional inducer and/or metabolite are induced in culture, e.g., grown in a flask, fermenter or other appropriate culture vessel, e.g., used during cell growth, cell expansion, fermentation, recovery, purification, formulation, and/or manufacture. In some embodiments, the promoter is directly or indirectly induced by a molecule that is added to in the bacterial culture to induce expression and pre-load the bacterium with one or more displayed proteins (e.g., viral, bacterial, fungal, and cancer protein), and/or immune modulator(s) and/or other polypeptide(s) of interest prior to administration. In some embodiments, the cultures, which are induced by a chemical and/or nutritional inducer and/or metabolite, are grown aerobically. In some embodiments, the cultures, which are induced by a chemical and/or nutritional inducer and/or metabolite, are grown anaerobically.

[0353] In one embodiment, the gene encoding the effector or the immune modulator is operably linked to a promoter that is induced by salicylate or a derivative thereof. After over 100 years of clinical use, salicylate remains one of the world's most extensively used `over-the-counter` drugs, and it is still recognized as the standard analgesic/antipyretic/anti-inflammatory agent by which newer drugs are assessed (Clissold; Salicylate and related derivatives of salicylic acid; Drugs. 1986; 32 Suppl 4:8-26). In an non-limiting example, the immune modulator is operably linked to a promoter PSal, as part of the salicylate PSal/NahR biosensor circuit (Part:BBa_J61051), originally adapted from Pseudomonas putida. The nahR gene was mined from the 83 kb naphthalene degradation plasmid NAH7 of Pseudomonas putida, encoding a 34 kDa protein which binds to nah and sal promoters to activate transcription in response to the inducer salicylate (Dunn, N. W., and I. C. Gunsalus (1973) Transmissible plasmid encoding early enzymes of naphthalene oxidation in Pseudomonas putida. J. Bacteriol. 114:974-979). In this system NahR is constitutively expressed by a constitutive promoter (Pc), and the expression of the protein of interest, e.g., the immune modulator is positively regulated by NahR in the presence of inducers (e.g., salicylate). Thus, in some embodiments, the genetically engineered bacteria comprise a gene sequence encoding an immune modulator which is operably linked to salicylate inducible promoter (e.g., PSal). In some embodiments, the genetically engineered bacteria further comprise gene sequence(s) encoding NahR, which are operably linked to a promoter. In some embodiments, NahR is under control of a constitutive promoter described herein or known in the art. In some embodiments, NahR is under control of an inducible promoter described herein or known in the art. In some embodiments described herein, the Biobrick BBa_J61051 (containing the gene encoding NahR driven by a constitutive promoter and the PSal promoter was cloned preceding dacA.

[0354] In one embodiment, expression of one or more immune modulator protein(s) of interest, e.g., one or more therapeutic polypeptide(s), is driven directly or indirectly by one or more salicylate inducible promoter(s).

[0355] In some embodiments, the salicylate inducible promoter is useful for or induced during in vivo expression of the one or more protein(s) of interest. In some embodiments, expression of one or more immune modulator protein(s) of interest is driven directly or indirectly by one or more salicylate inducible promoter(s) in vivo. In some embodiments, the promoter is directly or indirectly induced by a molecule that is co-administered with the genetically engineered bacteria of the invention, e.g., salicylate.

[0356] In some embodiments, salicylate is administered intranasally at a defined time before bacterial injection into the target site. In some embodiments, salicylate is administered intranasally at a defined time after bacterial injection into the target site. In some embodiments, salicylate is administered intranasally concurrently with bacterial injection into the target site. In some embodiments, salicylate is administered intravenously at a defined time before bacterial injection into the target site. In some embodiments, salicylate is administered intravenously at a defined time after bacterial injection into the target site. In some embodiments, salicylate is administered intravenously concurrently with bacterial injection into the target site. In some embodiments, salicylate is administered subcutaneously at a defined time before bacterial injection into the target site. In some embodiments, salicylate is administered subcutaneously at a defined time after bacterial injection into the target site. In some embodiments, salicylate is administered subcutaneously concurrently with bacterial injection into the target site.

[0357] In some embodiments, salicylate is administered intranasally at a defined time before bacterial injection into the target site. In some embodiments, salicylate is administered intranasally at a defined time after bacterial injection into the target site. In some embodiments, salicylate is administered intranasally concurrently with bacterial injection into the target site. In some embodiments, salicylate is administered intravenously at a defined time before bacterial injection into the target site. In some embodiments, salicylate is administered intravenously at a defined time after bacterial injection into the target site. In some embodiments, salicylate is administered intravenously concurrently with intravenous bacterial administration. In some embodiments, salicylate is administered subcutaneously at a defined time before bacterial injection into the target site. In some embodiments, salicylate is administered subcutaneously at a defined time after bacterial injection into the target site. In some embodiments, salicylate is administered subcutaneously concurrently with intravenous bacterial administration.

[0358] In some embodiments, expression of one or more protein(s) of interest, is driven directly or indirectly by one or more salicylate inducible promoter(s) during in vitro growth, preparation, or manufacturing of the strain prior to in vivo administration. In some embodiments, the salicylate inducible promoter(s) are induced in culture, e.g., grown in a flask, fermenter or other appropriate culture vessel, e.g., used during cell growth, cell expansion, fermentation, recovery, purification, formulation, and/or manufacture. In some embodiments, the promoter is directly or indirectly induced by a molecule that is added to in the bacterial culture to induce expression and pre-load the bacterium with the payload prior to administration, e.g., salicylate. In some embodiments, the cultures, which are induced by salicylate, are grown aerobically. In some embodiments, the cultures, which are induced by salicylate, are grown anaerobically.

[0359] In some embodiments, the salicylate inducible promoter drives the expression of one or more protein(s) of interest from a low-copy plasmid or a high copy plasmid or a biosafety system plasmid described herein. In some embodiments, the salicylate inducible promoter drives the expression of one or more protein(s) of interest from a construct which is integrated into the bacterial chromosome. Exemplary insertion sites are described herein.

[0360] In some embodiments, one or more protein(s) of interest are linked to and are driven by the native salicylate inducible promoter In some embodiments, the genetically engineered bacteria comprise one or more gene sequence(s) having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 1273 or SEQ ID NO: 1274.

[0361] In one embodiment, the genetically engineered bacteria comprise a gene sequence comprising SEQ ID NO: 1273 or SEQ ID NO: 1274. In another embodiment, the genetically engineered bacteria comprise a gene sequence which consists of SEQ ID NO: 1273 or SEQ ID NO: 1274.

[0362] In some embodiments, the salicylate inducible construct further comprises a gene encoding NahR, which in some embodiments is divergently transcribed from a constitutive or inducible promoter. In some embodiments, the genetically engineered bacteria comprise one or more gene sequence(s) having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 1278. In another embodiment, the genetically engineered bacteria comprise a gene sequence comprising SEQ ID NO: 1278. In another embodiment, the genetically engineered bacteria comprise a gene sequence which consists of SEQ ID NO: 1278.

[0363] In some embodiments, the genetically engineered bacteria comprise one or more gene sequence(s) encoding a polypeptide having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the polypeptide encoded by SEQ ID NO: 1280. In another embodiment, the genetically engineered bacteria comprise a gene sequence encoding a polypeptide comprising SEQ ID NO: 1280. In yet another embodiment, the polypeptide expressed by the genetically engineered bacteria consists of SEQ ID NO: 1280.

[0364] In one embodiment, the gene encoding the immune modulator is operably linked to a promoter that is induced by cumate or a derivative thereof. Suitable derivatives are known in the art and are for example described in U.S. Pat. No. 7,745,592. Benefits of cumate induction include that Cumate is non-toxic, water-soluble and inexpensive. The basic mechanism by which the cumate-regulated expression functions in the native P. putida F1 and how it is applied to other bacterial chassis, including but not limited to, E. coli has been previously described (see e.g., Choi et al., Novel, Versatile, and Tightly Regulated Expression System for Escherichia coli Strains; Appl. Environ. Microbiol. August 2010 vol. 76 no. 15 5058-5066). Essentially, the cumate circuit or switch includes four components: a strong promoter, a repressor-binding DNA sequence or operator, expression of cymR, a repressor, and cumate as the inducer. The addition of the inducer changes causes the formation of a complex between cumate and CymR and results in the removal of the repressor from its DNA binding site, allowing expression of the gene of interest. A construct comprising the cymR gene driven by a constitutive promoter and a cymR responsive promoter was cloned in front of the DacA gene to allow cumate inducible expression of DacA is described elsewhere herein.

[0365] In one embodiment, expression of one or more immune modulator protein(s) of interest, e.g., one or more therapeutic polypeptide(s), is driven directly or indirectly by one or more promoter(s) inducible by cumate or a derivative thereof.

[0366] In some embodiments, the cumate inducible promoter is useful for or induced during in vivo expression of the one or more protein(s) of interest. In some embodiments, expression of one or more immune modulator protein(s) of interest is driven directly or indirectly by one or more cumate inducible promoter(s) in vivo. In some embodiments, the promoter is directly or indirectly induced by a molecule that is co-administered with the genetically engineered bacteria of the invention, e.g., cumate.

[0367] In some embodiments, cumate is administered intranasally at a defined time before bacterial injection into the target site. In some embodiments, cumate is administered intranasally at a defined time after bacterial injection into the target site. In some embodiments, cumate is administered intranasally concurrently with bacterial injection into the target site. In some embodiments, cumate is administered intravenously at a defined time before bacterial injection into the target site. In some embodiments, cumate is administered intravenously at a defined time after bacterial injection into the target site. In some embodiments, cumate is administered intravenously concurrently with bacterial injection into the target site. In some embodiments, cumate is administered subcutaneously at a defined time before bacterial injection into the target site. In some embodiments, cumate is administered subcutaneously at a defined time after bacterial injection into the target site. In some embodiments, cumate is administered subcutaneously concurrently with bacterial injection into the target site.

[0368] In some embodiments, cumate is administered intranasally at a defined time before bacterial injection into the target site. In some embodiments, cumate is administered intranasally at a defined time after bacterial injection into the target site. In some embodiments, cumate is administered intranasally concurrently with bacterial injection into the target site. In some embodiments, cumate is administered intravenously at a defined time before bacterial injection into the target site. In some embodiments, cumate is administered intravenously at a defined time after bacterial injection into the target site. In some embodiments, cumate is administered intravenously concurrently with intravenous bacterial administration. In some embodiments, cumate is administered subcutaneously at a defined time before bacterial injection into the target site. In some embodiments, cumate is administered subcutaneously at a defined time after bacterial injection into the target site. In some embodiments, cumate is administered subcutaneously concurrently with intravenous bacterial administration

[0369] In some embodiments, expression of one or more protein(s) of interest, is driven directly or indirectly by one or more cumate inducible promoter(s) during in vitro growth, preparation, or manufacturing of the strain prior to in vivo administration. In some embodiments, the cumate inducible promoter(s) are induced in culture, e.g., grown in a flask, fermenter or other appropriate culture vessel, e.g., used during cell growth, cell expansion, fermentation, recovery, purification, formulation, and/or manufacture. In some embodiments, the promoter is directly or indirectly induced by a molecule that is added to in the bacterial culture to induce expression and pre-load the bacterium with the payload prior to administration, e.g., cumate. In some embodiments, the cultures, which are induced by cumate, are grown aerobically. In some embodiments, the cultures, which are induced by cumate, are grown anaerobically.

[0370] In some embodiments, the cumate inducible promoter drives the expression of one or more protein(s) of interest from a low-copy plasmid or a high copy plasmid or a biosafety system plasmid described herein. In some embodiments, the cumate inducible promoter drives the expression of one or more protein(s) of interest from a construct which is integrated into the bacterial chromosome. Exemplary insertion sites are described herein.

[0371] In some embodiments, one or more protein(s) of interest are operably linked to by the native cumate inducible promoter. In some embodiments, the genetically engineered bacteria comprise one or more gene sequence(s) having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 1270 or SEQ ID NO: 1271.

[0372] In one embodiment, the genetically engineered bacteria comprise a gene sequence comprising SEQ ID NO: 1270 or SEQ ID NO: 1271. In another embodiment, the genetically engineered bacteria comprise a gene sequence which consists of SEQ ID NO: 1270 or SEQ ID NO: 1271

[0373] In some embodiments, the cumate inducible construct further comprises a gene encoding CymR, which in some embodiments is divergently transcribed from a constitutive or inducible promoter. In some embodiments, the genetically engineered bacteria comprise one or more gene sequence(s) having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 1268. In another embodiment, the genetically engineered bacteria comprise a gene sequence comprising SEQ ID NO: 1268. In another embodiment, the genetically engineered bacteria comprise a gene sequence which consists of SEQ ID NO: 1268.

[0374] In some embodiments, the genetically engineered bacteria comprise one or more gene sequence(s) encoding a polypeptide having at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity with the polypeptide encoded by SEQ ID NO: 1269. In another embodiment, the genetically engineered bacteria comprise a gene sequence encoding a polypeptide comprising SEQ ID NO: 1269. In yet another embodiment, the polypeptide expressed by the genetically engineered bacteria consists of SEQ ID NO: 1269.

[0375] Other inducible promoters contemplated in the disclosure are described in are described in International Patent Application PCT/US2017/013072, filed Jan. 11, 2017, published as WO2017/123675, the contents of which is herein incorporated by reference in its entirety. Such promoters include arabinose inducible, rhamnose inducible, and IPTG inducible promoters, tetracycline inducible promoters, temperature inducible promoters, and PSSB promoter. These promoters can be used in combination with each other or with other inducible promoters, such as low oxygen inducible promoters, or constitutive promoters to fine tune expression of different effectors, e.g., in one bacterium or in a composition of more than one strain of bacteria.

Constitutive Promoters

[0376] In some embodiments, the gene encoding the payload is present on a plasmid and operably linked to a constitutive promoter. In some embodiments, the gene encoding the payload is present on a chromosome and operably linked to a constitutive promoter.

[0377] In some embodiments, the constitutive promoter is active under in vivo conditions, as described herein. In some embodiments, the promoters is active under in vitro conditions, e.g., various cell culture and/or cell manufacturing conditions, as described herein. In some embodiments, the constitutive promoter is active under in vivo conditions, as described herein, and under in vitro conditions, e.g., various cell culture and/or cell production and/or manufacturing conditions, as described herein.

[0378] In some embodiments, the constitutive promoter that is operably linked to the gene encoding the payload is active in various exogenous environmental conditions (e.g., in vivo and/or in vitro and/or production/manufacturing conditions).

[0379] In some embodiments, the constitutive promoter is active in exogenous environmental conditions specific to the target sites. In some embodiments, the constitutive promoter is active in exogenous environmental conditions specific to the pulmonary system of a mammal. In some embodiments, the constitutive promoter is active in the presence of molecules or metabolites that are specific to the pulmonary system of a mammal. In some embodiments, the constitutive promoter is directly or indirectly induced by a molecule that is co-administered with the bacterial cell. In some embodiments, the constitutive promoter is active in the presence of molecules or metabolites or other conditions, that are present during in vitro culture, cell production and/or manufacturing conditions. Bacterial constitutive promoters are known in the art and are described in are described in International Patent Application PCT/US2017/013072, filed Jan. 11, 2017, published as WO2017/123675, the contents of which is herein incorporated by reference in its entirety. Examples are included herein in SEQ ID NO: 598-739 and a subset is shown in Table 5.

TABLE-US-00005 TABLE 5 Promoters SEQ ID Name Description NO Plpp The Plpp promoter is a natural 740 promoter taken from the Nissle genome. In situ it is used to drive production of lpp, which is known to be the most abundant protein in the cell. Also, in some previous RNAseq experiments I was able to confirm that the lpp mRNA is one of the most abundant mRNA in Nissle during exponential growth. PapFAB46 See, e.g., Kosuri, S., 741 Goodman, D. B. & Cambray, G. Composability of regulatory sequences controlling transcription and translation in Escherichia coli. in 1-20 (2013). doi:10.1073/pnas. PJ23101 UP clement helps recruit 742 UP RNA polymerase element (gaaaaatttttttaaaaaaaaaac (SEQ ID NO: 1250)) PJ23107 UP clement helps recruit 743 UP RNA polymerase element (gaaaaatttttttaaaaaaaaaac (SEQ ID NO: 1250)) PSYN23119 UP element at 5' end; 744 consensus -10 region is TATAAT; the consensus -35 is TTGACA; the extended -10 region is generally TGNTATAAT (TGGTATAAT in this sequence)

[0380] In some embodiments, the promoter is Plpp or a derivative thereof. In some embodiments, the promoter comprises a sequence from SEQ ID NO:740. In some embodiments, the constitutive promoter is at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% homologous to the sequence of SEQ ID NO: 740. In some embodiments, the promoter is PapFAB46 or a derivative thereof. In some embodiments, the promoter comprises a sequence from SEQ ID NO:741. In some embodiments, the constitutive promoter is at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% homologous to the sequence of SEQ ID NO: 741. In some embodiments, the promoter is PJ23101+UP element or a derivative thereof. In some embodiments, the promoter comprises a sequence from SEQ ID NO:742. In some embodiments, the constitutive promoter is at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% homologous to the sequence of SEQ ID NO: 742. In some embodiments, the promoter is PJ23107+UP element or a derivative thereof. In some embodiments, the promoter comprises a sequence from SEQ ID NO:743. In some embodiments, the constitutive promoter is at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% homologous to the sequence of SEQ ID NO: 743. In some embodiments, the promoter is PSYN23119 or a derivative thereof. In some embodiments, the promoter comprises a sequence from SEQ ID NO:744. In some embodiments, the constitutive promoter is at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% homologous to the sequence of SEQ ID NO: 744.

[0381] Additional promoters which may be linked to the payload include apFAB124 (tcgacatttatcccttgcggcgaatacttacagccatagcaa (SEQ ID NO: 1443)); apfab338(GGCGCGCC TTGACAATTAATCATCCGGCTCCTAGGATGTGTGGAGGGAC (SEQ ID NO: 1444)), apFAB66 (GGCGCGCC TTGACATCAGGAAAATTTTTCTGTATAATAGATTCATCTCAA (SEQ ID NO: 1445)), and apFAB54 (GGCGCGCC TTGACATAAAGTCTAACCTATAGGATACTTACAGCCATACAAG (SEQ ID NO: 1446)). In some embodiments, the promoter is apFAB124 or a derivative thereof. In some embodiments, the promoter comprises a sequence of apFAB124. In some embodiments, the constitutive promoter is at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% homologous to the sequence of apFAB124. In some embodiments, the promoter is apFAB338 or a derivative thereof. In some embodiments, the promoter comprises a sequence of apFAB338. In some embodiments, the constitutive promoter is at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% homologous to the sequence of apFAB338. In some embodiments, the promoter is apFAB66 or a derivative thereof. In some embodiments, the promoter comprises a sequence of apFAB66. In some embodiments, the constitutive promoter is at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% homologous to the sequence of apFAB66. In some embodiments, the promoter is apFAB54 or a derivative thereof. In some embodiments, the promoter comprises a sequence of apFAB54. In some embodiments, the constitutive promoter is at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% homologous to the sequence of apFAB54.

Ribosome Binding Sites

[0382] In some embodiments, ribosome binding sites are added, switched out or replaced. By testing a few ribosome binding sites, expression levels can be fine-tuned to the desired level. In some embodiments, RBS which are suitable for prokaryotic expression and can be used to achieve the desired expression levels are selected. Non-limiting examples of RBS are listed at Registry of standard biological parts and are described in are described in International Patent Application PCT/US2017/013072, filed Jan. 11, 2017, published as WO2017/123675, the contents of which is herein incorporated by reference in its entirety. Suitable examples are shown in SEQ ID NO: 1018-1050 and 869-871, 873-877, 880-887.

Induction of Payloads During Strain Culture

[0383] Induction of payloads during culture is described in International Patent Application PCT/US2017/013072, filed Jan. 11, 2017, published as WO2017/123675, the contents of which is herein incorporated by reference in its entirety.

[0384] In some embodiments, it is desirable to pre-induce payload or protein of interest expression and/or payload activity prior to administration. Such payload or protein of interest may be an effector intended for secretion or may be an enzyme which catalyzes a metabolic reaction to produce an effector. In other embodiments, the protein of interest is an enzyme which catabolizes a harmful metabolite. In such situations, the strains are pre-loaded with active payload or protein of interest. In such instances, the genetically engineered bacteria of the invention express one or more protein(s) of interest, under conditions provided in bacterial culture during cell growth, expansion, purification, fermentation, and/or manufacture prior to administration in vivo. Such culture conditions can be provided in a flask, fermenter or other appropriate culture vessel, e.g., used during cell growth, cell expansion, fermentation, recovery, purification, formulation, and/or manufacture. As used herein, the term "bacterial culture" or bacterial cell culture" or "culture" refers to bacterial cells or microorganisms, which are maintained or grown in vitro during several production processes, including cell growth, cell expansion, recovery, purification, fermentation, and/or manufacture. As used herein, the term "fermentation" refers to the growth, expansion, and maintenance of bacteria under defined conditions. Fermentation may occur under a number of cell culture conditions, including anaerobic or low oxygen or oxygenated conditions, in the presence of inducers, nutrients, at defined temperatures, and the like.

[0385] Culture conditions are selected to achieve optimal activity and viability of the cells, while maintaining a high cell density (high biomass) yield. A number of cell culture conditions and operating parameters are monitored and adjusted to achieve optimal activity, high yield and high viability, including oxygen levels (e.g., low oxygen, microaerobic, aerobic), temperature of the medium, and nutrients and/or different growth media, chemical and/or nutritional inducers and other components provided in the medium.

[0386] In some embodiments, the one or more protein(s) of interest and are directly or indirectly induced, while the strains is grown up for in vivo administration. Without wishing to be bound by theory, pre-induction may boost in vivo activity. If the bacterial residence time in a particular pulmonary compartment is relatively short, the bacteria may pass through without reaching full in vivo induction capacity. In contrast, if a strain is pre-induced and preloaded, the strains are already fully active, allowing for greater activity more quickly as the bacteria reach the pulmonary system. Ergo, no transit time is "wasted", in which the strain is not optimally active. As the bacteria continue to move through the pulmonary system, in vivo induction occurs under environmental conditions of the pulmonary system. Similarly, systemic administration or intranasal delivery, as described herein, of other bacterium may allow for greater activity more quickly as the bacteria reach the target site.

[0387] In one embodiment, expression of one or more payload(s), is induced during cell growth, cell expansion, fermentation, recovery, purification, formulation, and/or manufacture. In one embodiment, expression of several different proteins of interest is induced during cell growth, cell expansion, fermentation, recovery, purification, formulation, and/or manufacture.

[0388] In some embodiments, the strains are administered without any pre-induction protocols during strain growth prior to in vivo administration.

Anaerobic Induction

[0389] In some embodiments, cells are induced under anaerobic or low oxygen conditions in culture. In such instances, cells are grown (e.g., for 1.5 to 3 hours) until they have reached a certain OD, e.g., ODs within the range of 0.1 to 10, indicating a certain density e.g., ranging from 1.times.10{circumflex over ( )}8 to 1.lamda.10{circumflex over ( )}11, and exponential growth and are then switched to anaerobic or low oxygen conditions for approximately 3 to 5 hours. In some embodiments, strains are induced under anaerobic or low oxygen conditions, e.g. to induce FNR promoter activity and drive expression of one or more payload(s) and/or transporters under the control of one or more FNR promoters.

[0390] In one embodiment, expression of one or more payload(s), is under the control of one or more FNR promoter(s) and is induced during cell growth, cell expansion, fermentation, recovery, purification, formulation, and/or manufacture under anaerobic or low oxygen conditions. In one embodiment, expression of several different proteins of interest is under the control of one or more FNR promoter(s) and is induced during cell growth, cell expansion, fermentation, recovery, purification, formulation, and/or manufacture under anaerobic or low oxygen conditions.

[0391] Without wishing to be bound by theory, strains that comprise one or more payload(s) under the control of an FNR promoter, may allow expression of payload(s) from these promoters in vitro, under anaerobic or low oxygen culture conditions, and in vivo.

[0392] In some embodiments, promoters linked to the payload of interest may be inducible by arabinose, cumate, and salicylate, IPTG, rhamnose, tetracycline, and/or other chemical and/or nutritional inducers can be induced under anaerobic or low oxygen conditions in the presence of the chemical and/or nutritional inducer. In particular, strains may comprise a combination of gene sequence(s), some of which are under control of FNR promoters and others which are under control of promoters induced by chemical and/or nutritional inducers. In some embodiments, strains may comprise one or more payload gene sequence(s) and/or under the control of one or more FNR promoter(s), and one or more payload gene sequence(s) under the control of a one or more constitutive promoter(s) described herein.

Aerobic Induction

[0393] In some embodiments, it is desirable to prepare, pre-load and pre-induce the strains under aerobic conditions. This allows more efficient growth and viability, and, in some cases, reduces the build-up of toxic metabolites. In such instances, cells are grown (e.g., for 1.5 to 3 hours) until they have reached a certain OD, e.g., ODs within the range of 0.1 to 10, indicating a certain density e.g., ranging from 1.times.10{circumflex over ( )}8 to 1.times.10 {circumflex over ( )}11, and exponential growth and are then induced through the addition of the inducer or through other means, such as shift to a permissive temperature, for approximately 3 to 5 hours.

[0394] In some embodiments, promoters inducible by arabinose, cumate, and salicylate, IPTG, rhamnose, tetracycline, and/or other chemical and/or nutritional inducers described herein or known in the art can be induced under aerobic conditions in the presence of the chemical and/or nutritional inducer during cell growth, cell expansion, fermentation, recovery, purification, formulation, and/or manufacture. In one embodiment, expression of one or more payload(s) is under the control of one or more promoter(s) regulated by chemical and/or nutritional inducers and is induced during cell growth, cell expansion, fermentation, recovery, purification, formulation, and/or manufacture under aerobic conditions.

[0395] In some embodiments, genetically engineered strains comprise gene sequence(s) which are induced under aerobic culture conditions. In some embodiments, these strains further comprise FNR inducible gene sequence(s) for in vivo activation. In some embodiments, these strains do not further comprise FNR inducible gene sequence(s) for in vivo activation.

Microaerobic Induction

[0396] In some embodiments, viability, growth, and activity are optimized by pre-inducing the bacterial strain under microaerobic conditions. In some embodiments, microaerobic conditions are best suited to "strike a balance" between optimal growth, activity and viability conditions and optimal conditions for induction; in particular, if the expression of the one or more payload(s) are driven by an anaerobic and/or low oxygen promoter, e.g., a FNR promoter. In such instances, cells are for example grown (e.g., for 1.5 to 3 hours) until they have reached a certain OD, e.g., ODs within the range of 0.1 to 10, indicating a certain density e.g., ranging from 1.times.10{circumflex over ( )}8 to 1.times.10{circumflex over ( )}11, and exponential growth and are then induced through the addition of the inducer or through other means, such as shift to at a permissive temperature, for approximately 3 to 5 hours.

[0397] In one embodiment, expression of one or more payload(s) is under the control of one or more FNR promoter(s) and is induced during cell growth, cell expansion, fermentation, recovery, purification, formulation, and/or manufacture under microaerobic conditions.

[0398] Without wishing to be bound by theory, strains that comprise one or more payload(s) under the control of an FNR promoter, may allow expression of payload(s) from these promoters in vitro, under microaerobic culture conditions, and in vivo, under the low oxygen conditions.

[0399] In some embodiments, promoters inducible by arabinose, cumate, and salicylate, IPTG, rhamnose, tetracycline, and/or other chemical and/or nutritional inducers can be induced under microaerobic conditions in the presence of the chemical and/or nutritional inducer. In particular, strains may comprise a combination of gene sequence(s), some of which are under control of FNR promoters and others which are under control of promoters induced by chemical and/or nutritional inducers. In some embodiments, strains may comprise one or more payload gene sequence(s) under the control of one or more FNR promoter(s), and one or more payload gene sequence(s) under the control of a one or more constitutive promoter(s) described herein.

[0400] In one embodiment, expression of one or more payload(s) is under the control of one or more promoter(s) regulated by chemical and/or nutritional inducers and is induced during cell growth, cell expansion, fermentation, recovery, purification, formulation, and/or manufacture under microaerobic conditions.

Induction of Strains Using Phasing, Pulsing and/or Cycling

[0401] In some embodiments, cycling, phasing, or pulsing techniques are employed during cell growth, expansion, recovery, purification, fermentation, and/or manufacture to efficiently induce and grow the strains prior to in vivo administration. This method is used to "strike a balance" between optimal growth, activity, cell health, and viability conditions and optimal conditions for induction; in particular, if growth, cell health or viability are negatively affected under inducing conditions. In such instances, cells are grown (e.g., for 1.5 to 3 hours) in a first phase or cycle until they have reached a certain OD, e.g., ODs within the range of 0.1 to 10, indicating a certain density e.g., ranging from 1.times.10{circumflex over ( )}8 to 1.times.10{circumflex over ( )}11, and are then induced through the addition of the inducer or through other means, such as shift to a permissive temperature (if a promoter is thermoregulated), or change in oxygen levels (e.g., reduction of oxygen level in the case of induction of an FNR promoter driven construct) for approximately 3 to 5 hours. In a second phase or cycle, conditions are brought back to the original conditions which support optimal growth, cell health and viability. Alternatively, if a chemical and/or nutritional inducer is used, then the culture can be spiked with a second dose of the inducer in the second phase or cycle.

[0402] In some embodiments, two cycles of optimal conditions and inducing conditions are employed (i.e., growth, induction, recovery and growth, induction). In some embodiments, three cycles of optimal conditions and inducing conditions are employed. In some embodiments, four or more cycles of optimal conditions and inducing conditions are employed. In a non-liming example, such cycling and/or phasing is used for induction under anaerobic and/or low oxygen conditions (e.g., induction of FNR promoters). In one embodiment, cells are grown to the optimal density and then induced under anaerobic and/or low oxygen conditions. Before growth and/or viability are negatively impacted due to stressful induction conditions, cells are returned to oxygenated conditions to recover, after which they are then returned to inducing anaerobic and/or low oxygen conditions for a second time. In some embodiments, these cycles are repeated as needed.

[0403] In some embodiments, growing cultures are spiked once with the chemical and/or nutritional inducer. In some embodiments, growing cultures are spiked twice with the chemical and/or nutritional inducer. In some embodiments, growing cultures are spiked three or more times with the chemical and/or nutritional inducer. In a non-limiting example, cells are first grown under optimal growth conditions up to a certain density, e.g., for 1.5 to 3 hour) to reach an of 0.1 to 10, until the cells are at a density ranging from 1.times.10{circumflex over ( )}8 to 1.times.10{circumflex over ( )}11. Then the chemical inducer, e.g., arabinose, cumate, and salicylate or IPTG, is added to the culture. After 3 to 5 hours, an additional dose of the inducer is added to re-initiate the induction. Spiking can be repeated as needed.

[0404] In some embodiments, payload(s) induced during cell growth, cell expansion, fermentation, recovery, purification, formulation, and/or manufacture by using phasing or cycling or pulsing or spiking techniques are under the control of different inducible promoters, for example two different chemical inducers. In other embodiments, the payload is induced under low oxygen conditions or microaerobic conditions and a second payload is induced by a chemical inducer.

Secretion

[0405] In any of the embodiments described herein, in which the genetically engineered microorganism produces a protein, polypeptide, peptide, or other immune modulatory, DNA, RNA, small molecule or other molecule intended to be secreted from the microorganism, such as a protein (e.g., viral, bacterial, fungal, and cancer protein) and/or STING agonist, the engineered microorganism may comprise a secretion mechanism and corresponding gene sequence(s) encoding the secretion system.

[0406] In some embodiments, the genetically engineered bacteria further comprise a native secretion mechanism or non-native secretion mechanism that is capable of secreting the immune modulator from the bacterial cytoplasm in the extracellular environment. Many bacteria have evolved sophisticated secretion systems to transport substrates across the bacterial cell envelope. Substrates, such as small molecules, proteins, and DNA, may be released into the extracellular space or periplasm (such as the gut lumen or other space), injected into a target cell, or associated with the bacterial membrane.

[0407] In Gram-negative bacteria, secretion machineries may span one or both of the inner and outer membranes. In order to translocate a protein, e.g., therapeutic polypeptide, to the extracellular space, the polypeptide must first be translated intracellularly, mobilized across the inner membrane and finally mobilized across the outer membrane. Many effector proteins (e.g., therapeutic polypeptides)--particularly those of eukaryotic origin--contain disulphide bonds to stabilize the tertiary and quaternary structures. While these bonds are capable of correctly forming in the oxidizing periplasmic compartment with the help of periplasmic chaperones, in order to translocate the polypeptide across the outer membrane the disulphide bonds must be reduced and the protein unfolded again.

[0408] Suitable secretion systems for secretion of heterologous polypeptides, e.g., effector molecules, from gram negative and gram positive bacteria are described in International Patent Application PCT/US2017/013072, filed Jan. 11, 2017, published as WO2017/123675, the contents of which is herein incorporated by reference in its entirety. Such secretion systems include Double membrane-spanning secretion systems include, but are not limited to, the type I secretion system (T1SS), the type II secretion system (T2SS), the type III secretion system (T3SS), the type IV secretion system (T4SS), the type VI secretion system (T6SS), and the resistance-nodulation-division (RND) family of multi-drug efflux pumps, and type VII secretion system (T7SS). Alternatively, hemolysin-based secretion systems, Type V autotransporter secretion systems, traditional or modified type III or a type III-like secretion systems (T3SS), a flagellar type III secretion pathway may be used. In some embodiments, non-native single membrane-spanning secretion systems, e.g. Tat or Tat-like systems or Sec or Sec like systems may be used. Any of the secretion systems described herein and in PCT/US2017/013072 may according to the disclosure be employed to secrete the polypeptides of interest.

[0409] One way to secrete properly folded proteins in gram-negative bacteria--particularly those requiring disulphide bonds--is to target the reducing-environment periplasm in conjunction with a destabilizing outer membrane. In this manner the protein is mobilized into the oxidizing environment and allowed to fold properly. In contrast to orchestrated extracellular secretion systems, the protein is then able to escape the periplasmic space in a correctly folded form by membrane leakage. These "leaky" gram-negative mutants are therefore capable of secreting bioactive, properly disulphide-bonded polypeptides. In some embodiments, the genetically engineered bacteria have a "leaky" or de-stabilized outer membrane (DOM). Destabilizing the bacterial outer membrane to induce leakiness can be accomplished by deleting or mutagenizing genes responsible for tethering the outer membrane to the rigid peptidoglycan skeleton, including for example, lpp, ompC, ompA, ompF, tolA, tolB, and pal. Lpp is the most abundant polypeptide in the bacterial cell existing at .about.500,000 copies per cell and functions as the primary `staple` of the bacterial cell wall to the peptidoglycan. TolA-PAL and OmpA complexes function similarly to Lpp and are other deletion targets to generate a leaky phenotype. Additionally, leaky phenotypes have been observed when periplasmic proteases are inactivated. The periplasm is very densely packed with protein and therefore encode several periplasmic proteins to facilitate protein turnover. Removal of periplasmic proteases such as degS, degP or nlpI can induce leaky phenotypes by promoting an excessive build-up of periplasmic protein. Mutation of the proteases can also preserve the effector polypeptide by preventing targeted degradation by these proteases.

[0410] Moreover, a combination of these mutations may synergistically enhance the leaky phenotype of the cell without major sacrifices in cell viability. Thus, in some embodiments, the engineered bacteria have one or more deleted or mutated membrane genes. In some embodiments, the engineered bacteria have a deleted or mutated lpp gene. In some embodiments, the engineered bacteria have one or more deleted or mutated gene(s), selected from ompA, ompA, and ompF genes. In some embodiments, the engineered bacteria have one or more deleted or mutated gene(s), selected from tolA, tolB, and pal genes. in some embodiments, the engineered bacteria have one or more deleted or mutated periplasmic protease genes. In some embodiments, the engineered bacteria have one or more deleted or mutated periplasmic protease genes selected from degS, degP, and nlpl. In some embodiments, the engineered bacteria have one or more deleted or mutated gene(s), selected from lpp, ompA, ompF, tolA, tolB, pal, degS, degP, and nlpl genes.

[0411] To minimize disturbances to cell viability, the leaky phenotype can be made inducible by placing one or more membrane or periplasmic protease genes, e.g., selected from lpp, ompA, ompF, tolA, tolB, pal, degS, degP, and nlpl, under the control of an inducible promoter. For example, expression of lpp or other cell wall stability protein or periplasmic protease can be repressed in conditions where the therapeutic polypeptide needs to be delivered (secreted). For instance, under inducing conditions a transcriptional repressor protein or a designed antisense RNA can be expressed which reduces transcription or translation of a target membrane or periplasmic protease gene. Conversely, overexpression of certain peptides can result in a destabilized phenotype, e.g., overexpression of colicins or the third topological domain of TolA, wherein peptide overexpression can be induced in conditions in which the therapeutic polypeptide needs to be delivered (secreted). These sorts of strategies would decouple the fragile, leaky phenotypes from biomass production. Thus, in some embodiments, the engineered bacteria have one or more membrane and/or periplasmic protease genes under the control of an inducible promoter.

[0412] In some embodiments in which the one or more proteins of interest or therapeutic proteins are secreted or exported from the microorganism, the engineered microorganism comprises gene sequence(s) that includes a secretion tag. In some embodiments, the one or more proteins of interest or therapeutic proteins include a "secretion tag" of either RNA or peptide origin to direct the one or more proteins of interest or therapeutic proteins to specific secretion systems. The secretion tag can be from the sec or the tat system.

[0413] In some embodiments, the genetically engineered bacterial comprise a native or non-native secretion system described herein for the secretion of an immune modulator, e.g., a cytokine, antibody (e.g., scFv), metabolic enzyme (e.g., kynureninase), and others described herein.

[0414] In some embodiments, the secretion tag is selected from PhoA, OmpF, cvaC, TorA, fdnG, dmsA, PelB, HlyA secretion signal, and HlyA secretion signal. In some embodiments, the secretion tag is the PhoA secretion signal. In some embodiments, the secretion tag comprises a sequence selected from SEQ ID NO: 745 or SEQ ID NO: 746. In some embodiments, the secretion tag is the OmpF secretion signal. In some embodiments, the secretion tag is the OmpF secretion signal. In some embodiments, the secretion tag comprises SEQ ID NO: 747. In some embodiments, the secretion tag is the cvaC secretion signal. In some embodiments, the secretion tag comprises SEQ ID NO: 748. In some embodiments, the secretion tag is the torA secretion signal. In some embodiments, the secretion tag comprises SEQ ID NO: 749. In some embodiments, the secretion tag is the fdnG secretion signal. In some embodiments, the secretion tag comprises SEQ ID NO: 750. In some embodiments, the secretion tag is the dmsA secretion signal. In some embodiments, the secretion tag comprises SEQ ID NO: 751. In some embodiments, the secretion tag is the PelB secretion signal. In some embodiments, the secretion tag comprises SEQ ID NO: 752. In some embodiments, the secretion tag is the HlyA secretion signal. In some embodiments, the secretion tag comprises a sequence selected from SEQ ID NO: 753 and SEQ ID NO: 754.

[0415] In some embodiments, the genetically engineered bacteria encode a polypeptide comprising a secretion tag selected from Adhesin (ECOLIN_19880), DsbA (ECOLIN_21525), GltI (ECOLIN_03430), GspD (ECOLIN_16495), HdeB (ECOLIN_19410), MalE (ECOLIN_22540), OppA (ECOLIN_07295), PelB, PhoA (ECOLIN_02255), PpiA (ECOLIN_18620), TolB, tort, OmpA, PelB, DsbA mglB, and lamB secretion tags. Exemplary sequences of secretion tags are shown in SEQ ID NO: 1222, SEQ ID NO: 1223, SEQ ID NO: 1224, SEQ ID NO: 1225, SEQ ID NO: 1226, SEQ ID NO: 1227, SEQ ID NO: 1228, SEQ ID NO: 1229, SEQ ID NO: 1230, SEQ ID NO: 1141, SEQ ID NO: 1142, SEQ ID NO: 1143, SEQ ID NO: 1144, SEQ ID NO: 1145, SEQ ID NO: 1253, SEQ ID NO: 1157, SEQ ID NO: 1158, SEQ ID NO: 1159, SEQ ID NO: 1160, SEQ ID NO: 1161, SEQ ID NO: 1162, SEQ ID NO: 1163, SEQ ID NO: 1164, SEQ ID NO: 1165, SEQ ID NO: 1166, and SEQ ID NO: 1167.

[0416] In some embodiments, a secretion tag polypeptide sequence may be selected from SEQ ID NO: 1218, SEQ ID NO: 1219, SEQ ID NO: 1181, SEQ ID NO: 1220, SEQ ID NO: 1221, SEQ ID NO: 1180, SEQ ID NO: 1184, SEQ ID NO: 1186, SEQ ID NO: 1190, SEQ ID NO: 1182, SEQ ID NO: 1135, SEQ ID NO: 1183, SEQ ID NO: 1188, SEQ ID NO: 1187, SEQ ID NO: 747, SEQ ID NO: 1185, and SEQ ID NO: 1189.

[0417] Any secretion tag or secretion system can be combined with any immune modulator described herein intended for secretion. In some embodiments, the secretion system is used in combination with one or more genomic mutations, which leads to the leaky or diffusible outer membrane phenotype (DOM), including but not limited to, lpp, nlP, tolA, PAL. In some embodiments, the therapeutic proteins secreted by the genetically engineered bacteria are modified to increase resistance to proteases, e.g. intestinal proteases.

[0418] In some embodiments, the therapeutic polypeptides of interest, e.g., the immune modulators, e.g., immune initiators and/or immune sustainers described herein, are secreted via a diffusible outer membrane (DOM) system. In some embodiments, the therapeutic polypeptide of interest is fused to a N-terminal Sec-dependent secretion signal. Non-limiting examples of such N-terminal Sec-dependent secretion signals include PhoA, OmpF, OmpA, and cvaC. In alternate embodiments, the therapeutic polypeptide of interest is fused to a Tat-dependent secretion signal. Exemplary Tat-dependent tags include TorA, FdnG, and DmsA.

[0419] In certain embodiments, the genetically engineered bacteria comprise deletions or mutations in one or more of the outer membrane and/or periplasmic proteins. Non-limiting examples of such proteins, one or more of which may be deleted or mutated, include lpp, pal, tolA, and/or nlpI. In some embodiments, lpp is deleted or mutated. In some embodiments, pal is deleted or mutated. In some embodiments, tolA is deleted or mutated. In other embodiments, nlpI is deleted or mutated. In yet other embodiments, certain periplasmic proteases are deleted or mutated, e.g., to increase stability of the polypeptide in the periplasm. Non-limiting examples of such proteases include degP and ompT. In some embodiments, degP is deleted or mutated. In some embodiments, ompT is deleted or mutated. In some embodiments, degP and ompT are deleted or mutated.

Surface Display

[0420] In some embodiments, the genetically engineered bacteria and/or microorganisms encode one or more gene(s) and/or gene cassette(s) encoding a display protein comprising an anchor domain, a linker, and a displayed protein (e.g., viral, bacterial, fungal, and cancer protein), and/or an immune modulator which is anchored or displayed on the surface of the bacteria and/or microorganisms.

[0421] In some embodiments, a viral spike protein is displayed as a viral protein on the surface of the bacteria and/or microorganisms. In other embodiments, the receptor binding domain (RBD) of a spike protein, e.g., a RBD of S protein from SARS-CoV-2, is displayed on the surface of the bacteria and/or microorganisms. Additional non-limiting examples of such viral proteins which may be produced by the bacteria of the disclosure include those peptides and/or epitopes described e.g., in Liu W J., et al. 2017, Antiviral Research 137:82-92; Huang J., et al. 2007, Vaccine 25: 6981-6991; Chen H., et al., 2005, J Immunol 175: 591-598; Ahmed S. F., et al., 2020, Viruses 12: 254; and Grifoni A., et al., Cell Host & Microbe 27: 1-10; the contents of each of which is herein incorporated by reference in its entirety or otherwise known in the art.

[0422] Examples of the immune modulators which are displayed or anchored to the bacteria and/or microorganism, are any of the immune modulators described herein, and include but are not limited to antibodies, e.g., scFv fragments, and tissue-specific antigens or neoantigens. In a non-limiting example, the antibodies or scFv fragments which are anchored or displayed on the bacterial cell surface are directed against checkpoint inhibitors described herein, including, but not limited to, CLTLA4, PD-1, PD-L1.

[0423] Suitable systems for surface display of heterologous polypeptides, e.g., effector molecules, on the surface of gram negative and gram positive bacteria are described in International Patent Application PCT/US2017/013072, filed Jan. 11, 2017, published as WO2017/123675, the contents of which is herein incorporated by reference in its entirety

[0424] In some embodiments, the genetically engineered bacteria comprise a gene sequence encoding a therapeutic polypeptide comprising an invasin display tag. In one embodiment, the genetically engineered bacteria comprise a gene sequence encoding a polypeptide comprising SEQ ID NO: 990.

[0425] In some embodiments, the genetically engineered bacteria comprise a gene sequence encoding a therapeutic polypeptide comprising an LppOmpA display tag. In one embodiment, the genetically engineered bacteria comprise a gene sequence encoding a polypeptide comprising SEQ ID NO: 991.

[0426] In some embodiments, the genetically engineered bacteria comprise a gene sequence encoding a therapeutic polypeptide comprising an intimin N display tag. In one embodiment, the genetically engineered bacteria comprise a gene sequence encoding a polypeptide comprising SEQ ID NO: 992.

[0427] In some embodiments, the genetically engineered bacteria comprise a display anchor which is at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% homologous to a sequence selected from SEQ ID NO: 990, SEQ ID NO: 991, and SEQ ID NO: 992. In another embodiment, the genetically engineered bacteria comprise a gene sequence encoding display anchor comprising a sequence selected from SEQ ID NO: 990, SEQ ID NO: 991, and SEQ ID NO: 992. In yet another embodiment, the display anchor expressed by the genetically engineered bacteria consists of a sequence selected from SEQ ID NO: 990, SEQ ID NO: 991, and SEQ ID NO: 992.

[0428] In some embodiments, one or more ScFvs are displayed on the bacterial cell surface, alone or in combination with other therapeutic polypeptides of interest.

[0429] In some embodiments, a cell surface display strategy or circuit is combined with a secretion strategy or circuit in one bacterium. In some embodiments, the same polypeptide is both displayed and secreted. In some embodiments, a first polypeptide is displayed and a second is secreted. In some embodiments, a display strategy or circuit strategy is combined with a circuit for the intracellular production of an enzyme and consequentially intracellular catabolism of its substrate. In some embodiments, a display strategy or display circuit is combined with a circuit for the intracellular production of a gut barrier enhancer molecule and/or an anti-inflammatory effector molecule.

[0430] In some embodiments, the expression of the surface displayed polypeptide or fusion protein is driven by an inducible promoter. In alternate embodiments, expression of the surface displayed polypeptides or polypeptide fusion proteins is driven by a constitutive promoter.

[0431] In some embodiments, the expression of the surface displayed polypeptide or fusion protein is plasmid based. In some embodiments, the gene sequence(s) encoding the antibodies or scFv fragments for surface display is chromosomally inserted.

Essential Genes, Auxotrophs, Kill Switches, and Host-Plasmid Dependency

[0432] As used herein, the term "essential gene" refers to a gene that is necessary to for cell growth and/or survival. Bacterial essential genes are well known to one of ordinary skill in the art, and can be identified by directed deletion of genes and/or random mutagenesis and screening (see, for example, Zhang and Lin, 2009, DEG 5.0, a database of essential genes in both prokaryotes and eukaryotes, Nucl. Acids Res., 37:D455-D458 and Gerdes et al., Essential genes on metabolic maps, Curr. Opin. Biotechnol., 17(5):448-456, the entire contents of each of which are expressly incorporated herein by reference).

[0433] An "essential gene" may be dependent on the circumstances and environment in which an organism lives. For example, a mutation of, modification of, or excision of an essential gene may result in the recombinant bacteria of the disclosure becoming an auxotroph. An auxotrophic modification is intended to cause bacteria to die in the absence of an exogenously added nutrient essential for survival or growth because they lack the gene(s) necessary to produce that essential nutrient.

[0434] An auxotrophic modification is intended to cause bacteria to die in the absence of an exogenously added nutrient essential for survival or growth because they lack the gene(s) necessary to produce that essential nutrient. In some embodiments, any of the genetically engineered bacteria described herein also comprise a deletion or mutation in a gene required for cell survival and/or growth. In one embodiment, the essential gene is a DNA synthesis gene, for example, thyA. In another embodiment, the essential gene is a bacterial cell wall synthesis gene, for example, dapA. In yet another embodiment, the essential gene is an amino acid gene, for example, serA or metA. Any gene required for cell survival and/or growth may be targeted, including but not limited to, cysE, glnA, ilvD, leuB, lysA, serA, metA, glyA, hisB, ilvA, pheA, proA, thrC, trpC, tyrA, thyA, uraA, dapA, dapB, dapD, dapE, dapF, flhD, metB, metC, proAB, and thil, as long as the corresponding wild-type gene product is not produced in the bacteria. Exemplary bacterial genes which may be disrupted or deleted to produce an auxotrophic strain as described in International Patent Application PCT/US2017/013072, filed Jan. 11, 2017, published as WO2017/123675, the contents of which is herein incorporated by reference in its entirety. These include, but are not limited to, genes required for oligonucleotide synthesis, amino acid synthesis, and cell wall synthesis. Table 6 lists exemplary bacterial genes which may be disrupted or deleted to produce an auxotrophic strain. These include, but are not limited to, genes required for oligonucleotide synthesis, amino acid synthesis, and cell wall synthesis.

TABLE-US-00006 TABLE 6 Non-limiting Examples of Bacterial Genes Useful for Generation of an Auxotroph Amino Acid Oligonucleotide Cell Wall cysE thyA dapA glnA uraA dapB ilvD dapD leuB dapE lysA dapF serA metA glyA hisB ilvA pheA proA thrC trpC tyrA

[0435] Auxotrophic mutations are useful in some instances in which biocontainment strategies may be required to prevent unintended proliferation of the genetically engineered bacterium in a natural ecosystem. Any auxotrophic mutation in an essential gene described above or known in the art can be useful for this purpose, e.g. DNA synthesis genes, amino acid synthesis genes, or genes for the synthesis of cell wall. Accordingly, in some embodiments, the genetically engineered bacteria comprise modifications, e.g., mutation(s) or deletion(s) in one or more auxotrophic genes, e.g., to prevent growth and proliferation of the bacterium in the natural environment. In some embodiments, the modification may be located in a non-coding region. In some embodiments, the modifications result in attenuation of transcription or translation. In some embodiments, the modifications, e.g., mutations or deletions, result in reduced or no transcription or reduced or no translation of the essential gene. In some embodiments, the modifications, e.g., mutations or deletions, result in transcription and/or translation of a non-functional version of the essential gene. In some embodiments, the modifications, e.g., mutations or deletions result in in truncated transcription or translation of the essential gene, resulting in a truncated polypeptide. In some embodiments, the modification, e.g., mutation is located within the coding region of the gene.

[0436] While unable to grow in the natural ecosystem, certain auxotrophic mutations may allow growth and proliferation in the mammalian host administered the bacteria. For example, an essential pathway that is rendered non-functional by the auxotrophic mutation may be complemented by production of the metabolite by the host. As a result, the bacterium administered to the host can take up the metabolite from the environment and can proliferate and colonize the target site. Thus, in some embodiments, the auxotrophic gene is an essential gene for the production of a metabolite, which is also produced by the mammalian host in vivo. In some embodiments, metabolite production by the host may allow uptake of the metabolite by the bacterium and permit survival and/or proliferation of the bacterium within the target site. In some embodiments, bacteria comprising such auxotrophic mutations are capable of proliferating and colonizing the target site to the same extent as a bacterium of the same subtype which does not carry the auxotrophic mutation.

[0437] In some embodiments, the bacteria are capable of colonizing and proliferating in the target microenvironment. In some embodiments, the target colonizing bacteria comprise one or more auxotrophic mutations. In some embodiments, the target colonizing bacteria do not comprise one or more auxotrophic modifications or mutations. In a non-limiting example, greater numbers of bacteria are detected after 24 hours and 72 hours than were originally injected into the subject. In some embodiments, CFUs detected 24 hours post injection are at least about 1 to 2 logs greater than administered. In some embodiments, CFUs detected 24 hours post injection are at least about 2 to 3 logs greater than administered. In some embodiments, CFUs detected 24 hours post injection are at least about 3 to 4 logs greater than administered. In some embodiments, CFUs detected 24 hours post injection are at least about 4 to 5 logs greater than administered. In some embodiments, CFUs detected 24 hours post injection are at least about 5 to 6 logs greater than administered. In some embodiments, CFUs detected 72 hours post injection are at least about 1 to 2 logs greater than administered. In some embodiments, CFUs detected 72 hours post injection are at least about 2 to 3 logs greater than administered. In some embodiments, CFUs detected 72 hours post injection are at least about 3 to 4 logs greater than administered. In some embodiments, CFUs detected 72 hours post injection are at least about 4 to 5 logs greater than administered. In some embodiments, CFUs detected 72 hours post injection are at least about 5 to 6 logs greater than administered. In some embodiments, CFUs can be measured at later time points, such as after at least one week, after at least 2 or more weeks, after at least one month, after at least two or more months post injection.

[0438] Non-limiting examples of such auxotrophic genes, which allow proliferation and colonization of the target, are thyA and uraA, as shown herein. Accordingly, in some embodiments, the genetically engineered bacteria of the disclosure may comprise an auxotrophic modification, e.g., mutation or deletion, in the thyA gene. In some embodiments, the genetically engineered bacteria of the disclosure may comprise an auxotrophic modification, e.g., mutation or deletion, in the uraA gene. In some embodiments, the genetically engineered bacteria of the disclosure may comprise auxotrophic modification, e.g., mutation or deletion, in the thyA gene and the uraA gene.

[0439] Alternatively, the auxotrophic gene is an essential gene for the production of a metabolite which cannot be produced by the host within the target, i.e., the auxotrophic mutation is not complemented by production of the metabolite by the host within the target microenvironment. As a result, the this mutation may affect the ability of the bacteria to grow and colonize the target and bacterial counts decrease over time. This type of auxotrophic mutation can be useful for the modulation of in vivo activity of the immune modulator or duration of activity of the immune modulator, e.g., within a target. An example of this method of fine-tuning levels and timing of immune modulator release is described herein using a auxotrophic modification, e.g., mutation, in dapA. Diaminopimelic acid (Dap) is a characteristic component of certain bacterial cell walls, e.g., of gram negative bacteria. Without diaminopimelic acid, bacteria are unable to form proteoglycan, and as such are unable to grow. DapA is not produced by mammalian cells, and therefore no alternate source of DapA is provided in the target. As such, a dapA auxotrophy may present a particularly useful strategy to modulate and fine tune timing and extent of bacterial presence in the target and/or levels and timing of immune modulator expression and production. Accordingly, in some embodiments, the genetically engineered bacteria of the disclosure comprise an mutation in an essential gene for the production of a metabolite which cannot be produced by the host within the target. In some embodiments, the auxotrophic mutation is in a gene which is essential for the production and maintenance of the bacterial cell wall known in the art or described herein, or a mutation in a gene that is essential to another structure that is unique to bacteria and not present in mammalian cells. In some embodiments, bacteria comprising such auxotrophic mutations are capable of proliferating and colonizing the target to a substantially lesser extent than a bacterium of the same subtype which does not carry the auxotrophic mutation. Control of bacterial growth (and by extent effector levels) may be further combined with other regulatory strategies, including but not limited to, metabolite or chemically inducible promoters described herein.

[0440] In a non-limiting example, lower numbers of bacteria are detected after 24 hours and 72 hours than were originally injected into the subject. In some embodiments, CFUs detected 24 hours post injection are at least about 1 to 2 logs lower than administered. In some embodiments, CFUs detected 24 hours post injection are at least about 2 to 3 logs lower than administered. In some embodiments, CFUs detected 24 hours post injection are at least about 3 to 4 logs lower than administered. In some embodiments, CFUs detected 24 hours post injection are at least about 4 to 5 logs lower than administered. In some embodiments, CFUs detected 24 hours post injection are at least about 5 to 6 logs lower than administered. In some embodiments, CFUs detected 72 hours post injection are at least about 1 to 2 logs lower than administered. In some embodiments, CFUs detected 72 hours post injection are at least about 2 to 3 logs lower than administered. In some embodiments, CFUs detected 72 hours post injection are at least about 3 to 4 logs lower than administered. In some embodiments, CFUs detected 72 hours post injection are at least about 4 to 5 logs lower than administered. In some embodiments, CFUs detected 72 hours post injection are at least about 5 to 6 logs lower than administered. In some embodiments, CFUs can be measured at later time points, such as after at least one week, after at least 2 or more weeks, after at least one month, after at least two or more months post injection.

[0441] In some embodiments, the genetically engineered bacteria of the disclosure comprise a auxotrophic modification, e.g., mutation, in dapA. A non-limiting example described herein is a genetically engineered bacterium comprising gene sequences encoding dacA for c-di-AMP production. Production of the STING agonist can be temporally regulated or restricted through the introduction of a dapA auxotrophy. In some embodiments, the dapA auxotrophy provides a means for tunable STING agonist production.

[0442] Auxotrophic modifications may also be used to screen for mutant bacteria that produce the effector molecule for various applications. In one example, the auxotrophy is useful to monitor purity or "sterility" of batches in small and large scale production of a bacterial strain. In this case, the auxotrophy presents a means to distinguish the engineered bacterium from a potential contaminant. In a non-limiting example, during the manufacturing process of the live biotherapeutic (i.e., large scale), an auxotrophy can be a useful tool to demonstrate purity or "sterility" of the drug substance. This method to determine purity of the culture is particularly useful in the absence of an antibiotic resistance gene, which is often used for this purpose in experimental strains, but which may be removed during the development of the live therapeutic drug product.

[0443] trpE is another auxtrophic mutation described herein. Bacteria carrying this mutation cannot produce tryptophan. Genetically engineered bacteria described herein with a trpE mutation further comprise kynureninase. Kynureninase allows the bacterium to convert kynurenine into the tryptophan precursor anthranilate and therefore the bacterium can grow in the absence of tryptophan if kynurenine is present.

[0444] In some embodiments, the genetically engineered bacteria comprise auxotrophic mutation(s) in one essential gene. In some embodiments, the genetically engineered bacteria comprise auxotrophic mutation(s) in two essential genes (double auxotrophy). In some embodiments, the genetically engineered bacteria comprise auxotrophic mutation(s) in three or more essential gene(s).

[0445] In some embodiments, the genetically engineered bacteria comprise auxotrophic mutation(s) in dapA and thyA. In some embodiments, the genetically engineered bacteria comprise auxotrophic mutation(s) in dapA and uraA. In some embodiments, the genetically engineered bacteria comprise auxotrophic mutation(s) in thyA and uraA. In some embodiments, the genetically engineered bacteria comprise auxotrophic mutation(s) in dapA, thyA and uraA.

[0446] In some embodiments, the genetically engineered bacteria comprise auxotrophic mutation(s) in trpE. In some embodiments, the genetically engineered bacteria comprise auxotrophic mutation(s) in trpE and thyA. In some embodiments, the genetically engineered bacteria comprise auxotrophic mutation(s) in trpE and dapA. In some embodiments, the genetically engineered bacteria comprise auxotrophic mutation(s) in trpE and uraA. In some embodiments, the genetically engineered bacteria comprise auxotrophic mutation(s) in trpE, dapA and thyA. In some embodiments, the genetically engineered bacteria comprise auxotrophic mutation(s) in trpE, dapA and uraA. In some embodiments, the genetically engineered bacteria comprise auxotrophic mutation(s) in trpE, thyA and uraA. In some embodiments, the genetically engineered bacteria comprise auxotrophic mutation(s) in trpE, dapA, thyA and uraA.

[0447] In another non-limiting example, a conditional auxotroph can be generated. The chromosomal copy of dapA or thyA is knocked out. Another copy of thyA or dapA is introduced, e.g., under control of a low oxygen promoter. Under anaerobic conditions, dapA or thyA--as the case may be--are expressed, and the strain can grow in the absence of dap or thymidine. Under aerobic conditions, dapA or thyA expression is shut off, and the strain cannot grow in the absence of dap or thymidine. Such a strategy can also be employed to allow survival of bacteria under anaerobic conditions, e.g., the gut or conditions of the target microenvironment, but prevent survival under aerobic conditions.

[0448] In some embodiments, the genetically engineered bacterium of the present disclosure is a synthetic ligand-dependent essential gene (SLiDE) bacterial cell. SLiDE bacterial cells are synthetic auxotrophs with a mutation in one or more essential genes that only grow in the presence of a particular ligand (see Lopez and Anderson "Synthetic Auxotrophs with Ligand-Dependent Essential Genes for a BL21 (DE3 Biosafety Strain, "ACS Synthetic Biology (2015) DOI: 10.1021/acssynbio.5b00085, the entire contents of which are expressly incorporated herein by reference). SLiDE bacterial cells are described in International Patent Application PCT/US2017/013072, filed Jan. 11, 2017, published as WO2017/123675, the contents of which is herein incorporated by reference in its entirety.

[0449] In some embodiments, the genetically engineered bacteria of the invention also comprise a kill switch. Suitable kill switches are described in International Patent Application PCT/US2016/39427, filed Jun. 24, 2016, published as WO2016/210373, the contents of which are herein incorporated by reference in their entirety. The kill switch is intended to actively kill engineered microbes in response to external stimuli. As opposed to an auxotrophic mutation where bacteria die because they lack an essential nutrient for survival, the kill switch is triggered by a particular factor in the environment that induces the production of toxic molecules within the microbe that cause cell death.

[0450] In some embodiments, the genetically engineered bacteria of the invention also comprise a plasmid that has been modified to create a host-plasmid mutual dependency. In certain embodiments, the mutually dependent host-plasmid platform is as described in Wright et al., 2015. These and other systems and platforms are described in International Patent Application PCT/US2017/013072, filed Jan. 11, 2017, published as WO2017/123675, the contents of which is herein incorporated by reference in its entirety.

Genetic Regulatory Circuits

[0451] In some embodiments, the genetically engineered bacteria comprise multi-layered genetic regulatory circuits for expressing the constructs described herein. Suitable multi-layered genetic regulatory circuits are described in International Patent Application PCT/US2016/39434, filed on Jun. 24, 2016, published as WO2016/210378, the contents of which is herein incorporated by reference in its entirety. The genetic regulatory circuits are useful to screen for mutant bacteria that produce an immune modulator or rescue an auxotroph. In certain embodiments, the invention provides methods for selecting genetically engineered bacteria that produce one or more genes of interest.

Pharmaceutical Compositions and Formulations

[0452] Pharmaceutical compositions comprising the genetically engineered microorganisms of the invention may be used to treat, manage, ameliorate, and/or prevent viral infection, e.g., the coronavirus disease 2019 (COVID-19). Pharmaceutical compositions of the invention comprising one or more genetically engineered bacteria, alone or in combination with prophylactic agents, therapeutic agents, and/or pharmaceutically acceptable carriers are provided.

[0453] In certain embodiments, the pharmaceutical composition comprises one species, strain, or subtype of bacteria that are engineered to comprise the genetic modifications described herein, e.g., one or more genes encoding one or more viral protein, e.g., a spike protein of SARV-CoV-2, and one or more effectors, e.g., immune modulators. In alternate embodiments, the pharmaceutical composition comprises two or more species, strains, and/or subtypes of bacteria that are each engineered to comprise the genetic modifications described herein, e.g., one or more genes encoding one or more effectors, e.g., immune modulators.

[0454] In some embodiments, the genetically engineered bacteria are administered systemically. In some embodiments, the genetically engineered bacteria are administered intranasally. The pharmaceutical compositions of the invention may be formulated in a conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries, which facilitate processing of the active ingredients into compositions for pharmaceutical use. Methods of formulating pharmaceutical compositions are known in the art (see, e.g., "Remington's Pharmaceutical Sciences," Mack Publishing Co., Easton, Pa.). In some embodiments, the pharmaceutical compositions are subjected to tableting, lyophilizing, direct compression, conventional mixing, dissolving, granulating, levigating, emulsifying, encapsulating, entrapping, or spray drying to form tablets, granulates, nanoparticles, nanocapsules, microcapsules, microtablets, pellets, or powders, which may be enterically coated or uncoated. Appropriate formulation depends on the route of administration.

[0455] The genetically engineered microorganisms may be formulated into pharmaceutical compositions in any suitable dosage form (e.g., liquids, capsules, sachet, hard capsules, soft capsules, tablets, enteric coated tablets, suspension powders, granules, or matrix sustained release formations for oral administration) and for any suitable type of administration (e.g., oral, topical, injectable, intravenous, sub-cutaneous, intranasal, intratumoral, peritumor, immediate-release, pulsatile-release, delayed-release, or sustained release). Suitable dosage amounts for the genetically engineered bacteria may range from about 10.sup.4 to 10.sup.12 bacteria. The composition may be administered once or more daily, weekly, or monthly. The composition may be administered before, during, or following a meal. In one embodiment, the pharmaceutical composition is administered before the subject eats a meal. In one embodiment, the pharmaceutical composition is administered currently with a meal. In on embodiment, the pharmaceutical composition is administered after the subject eats a meal.

[0456] The genetically engineered bacteria may be formulated into pharmaceutical compositions comprising one or more pharmaceutically acceptable carriers, thickeners, diluents, buffers, buffering agents, surface active agents, neutral or cationic lipids, lipid complexes, liposomes, penetration enhancers, carrier compounds, and other pharmaceutically acceptable carriers or agents. For example, the pharmaceutical composition may include, but is not limited to, the addition of calcium bicarbonate, sodium bicarbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, gelatin, vegetable oils, polyethylene glycols, and surfactants, including, for example, polysorbate 20. In some embodiments, the genetically engineered bacteria of the invention may be formulated in a solution of sodium bicarbonate, e.g., 1 molar solution of sodium bicarbonate (to buffer an acidic cellular environment, such as the stomach, for example). The genetically engineered bacteria may be administered and formulated as neutral or salt forms. Pharmaceutically acceptable salts include those formed with anions such as those derived from hydrochloric, phosphoric, acetic, oxalic, tartaric acids, etc., and those formed with cations such as those derived from sodium, potassium, ammonium, calcium, ferric hydroxides, isopropylamine, triethylamine, 2-ethylamino ethanol, histidine, procaine, etc.

[0457] The genetically engineered microorganisms may be administered intravenously, e.g., by infusion or injection. In other embodiments, the genetically engineered microorganisms may be administered intra-arterially, intramuscularly, or intraperitoneally. In some embodiments, the genetically engineered bacteria colonize about 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90% or more of the target.

[0458] The genetically engineered microorganisms of the disclosure may be administered via intranasal delivery, resulting in bacteria or virus that is directly deposited within the target site. Intranasal delivery of the engineered bacteria or virus may elicit a potent localized inflammatory response as well as an adaptive immune response against the target cells. Bacteria or virus are suspended in solution before being withdrawn into a 1-ml syringe.

[0459] Single insertion points or multiple insertion points can be used in percutaneous injection protocols. Using a single insertion point, the solution may be injected percutaneously along multiple tracks, as far as the radial reach of the needle allows. In other embodiments, multiple injection points may be used if the target is larger than the radial reach of the needle. The needle can be pulled back without exiting, and redirected as often as necessary until the full dose is injected and dispersed. To maintain sterility, a separate needle is used for each injection. Needle size and length varies depending on the tissue type.

[0460] In some embodiments, the target site is injected percutaneously with an 18-gauge multipronged needle (Quadra-Fuse, Rex Medical). The device consists of an 18 gauge puncture needle 20 cm in length. The needle has three retractable prongs, each with four terminal side holes and a connector with extension tubing clamp. The prongs are deployed from the lateral wall of the needle. The needle can be introduced percutaneously into the center of the target and can be positioned at the deepest margin of the target. The prongs are deployed to the margins of the target. The prongs are deployed at maximum length and then are retracted at defined intervals. Optionally, one or more rotation-injection-rotation maneuvers can be performed, in which the prongs are retracted, the needle is rotated by a 60 degrees, which is followed by repeat deployment of the prongs and additional injection.

[0461] In some embodiments, bacteria, e.g., E. coli Nissle, or spores, e.g., Clostridium novyi NT, are dissolved in sterile phosphate buffered saline (PBS) for systemic injection.

[0462] In some embodiments, the treatment regimen will include one or more intranasal administrations. In some embodiments, a treatment regimen will include an initial dose, which followed by at least one subsequent dose. One or more doses can be administered sequentially in two or more cycles.

[0463] For example, a first dose may be administered at day 1, and a second dose may be administered after 1, 2, 3, 4, 5, 6, days or 1, 2, 3, or 4 weeks or after a longer interval. Additional doses may be administered after 1, 2, 3, 4, 5, 6, days or after 1, 2, 3, or 4 weeks or longer intervals. In some embodiments, the first and subsequent administrations have the same dosage. In other embodiments, different doses are administered. In some embodiments, more than one dose is administered per day, for example, two, three or more doses can be administered per day.

[0464] The routes of administration and dosages described are intended only as a guide. The optimum route of administration and dosage can be readily determined by a skilled practitioner. The dosage may be determined according to various parameters, especially according to the location of the target, the size of the target, the age, weight and condition of the patient to be treated and the route and method of administration.

[0465] In one embodiment, Clostridium spores are delivered systemically. In another embodiment, Clostridium spores are delivered via intranasal delivery. In one embodiment, E. coli Nissle are delivered via intranasal delivery. In other embodiments, E. coli Nissle is administered via intravenous injection or orally, as described in a mouse model in for example in Danino et al. 2015, or Stritzker et al., 2007, the contents of which is herein incorporated by reference in its entirety. E. coli Nissle mutations to reduce toxicity include but are not limited to msbB mutants resulting in non-myristoylated LPS and reduced endotoxin activity, as described in Stritzker et al., 2010 (Stritzker et al, Bioengineered Bugs 1:2, 139-145; Myristylation negative msbB-mutants of probiotic E. coli Nissle 1917 retain tissue specific colonization properties but show less side effects in immunocompetent mice.

[0466] For intravenous injection a preferred dose of bacteria is the dose in which the greatest number of bacteria is found in the target tissue and the lowest amount found in other tissues. In mice, Stritzker et al (International Journal of Medical Microbiology 297 (2007) 151-162; Tissue specific colonization, tissue distribution, and gene induction by Escherichia coli Nissle 1917 in live mice) found that the lowest number of bacteria needed for successful target colonization was 2e4 CFU, in which half of the mice showed target colonization. Injection of 2e5 and 2e6 CFU resulted in colonization of all targets, and numbers of bacteria in the targets increased. However, at higher concentrations, bacterial counts became detectable in the liver and the spleen.

[0467] In some embodiments, the microorganisms of the disclosure may be administered orally. In one embodiment, the genetically engineered microorganism is delivered intranasally. In one embodiment, the genetically engineered microorganisms is delivered intrapleurally. In one embodiment, the genetically engineered microorganism is delivered subcutaneously. In one embodiment, the genetically engineered microorganism is delivered intravenously. In one embodiment, the genetically engineered microorganism is delivered intrapleurally.

[0468] In some embodiments, the genetically engineered microorganisms of the invention may be administered intranasally according to a regimen which requires multiple injections. In some embodiments, the same bacterial strains are administered in each injection. In some embodiments, a first strain is injected first and a second strain is injected at a later timepoint. For example, a strain capable of producing an immune initiator, e.g., STING agonist, may be administered concurrently or sequentially with a strain capable of producing another immune initiator, e.g., a co-stimulatory molecule, e.g., agonistic anti-OX40, 41BB, or GITR. Additional injections of the two immune initiators, either concurrently or sequentially, can follow. In another example, a strain capable of producing an immune initiator, e.g., STING agonist, may be administered first, and a strain capable of producing an immune sustainer, e.g., kynurenine consumption, or anti-PD-1/anti-PD-L1 secretion or anti-PD-1/anti-PD-L1 surface display, may be administered second. Additional injections of STING agonist producing strains and/or anti-PD-1/anti-PD-L1 producing strains can follow. Optionally, antibiotics can be used to clear a first strain from the target before injection of a second strain. Alternatively, an auxotrophic modification, e.g., mutation in the dapA gene, which limits colonization, can be incorporated into the first strain, which may eliminate the bacteria of the first strain prior to injection of a second strain.

[0469] The genetically engineered microorganisms disclosed herein may be administered topically and formulated in the form of an ointment, cream, transdermal patch, lotion, gel, shampoo, spray, aerosol, solution, emulsion, or other form well known to one of skill in the art. See, e.g., "Remington's Pharmaceutical Sciences," Mack Publishing Co., Easton, Pa. In an embodiment, for non-sprayable topical dosage forms, viscous to semi-solid or solid forms comprising a carrier or one or more excipients compatible with topical application and having a dynamic viscosity greater than water are employed. Suitable formulations include, but are not limited to, solutions, suspensions, emulsions, creams, ointments, powders, liniments, salves, etc., which may be sterilized or mixed with auxiliary agents (e.g., preservatives, stabilizers, wetting agents, buffers, or salts) for influencing various properties, e.g., osmotic pressure. Other suitable topical dosage forms include sprayable aerosol preparations wherein the active ingredient in combination with a solid or liquid inert carrier, is packaged in a mixture with a pressurized volatile (e.g., a gaseous propellant, such as freon) or in a squeeze bottle. Moisturizers or humectants can also be added to pharmaceutical compositions and dosage forms. Examples of such additional ingredients are well known in the art. In one embodiment, the pharmaceutical composition comprising the recombinant bacteria of the invention may be formulated as a hygiene product. For example, the hygiene product may be an antibacterial formulation, or a fermentation product such as a fermentation broth. Hygiene products may be, for example, shampoos, conditioners, creams, pastes, lotions, and lip balms.

[0470] The genetically engineered microorganisms disclosed herein may be administered orally and formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, etc. Pharmacological compositions for oral use can be made using a solid excipient, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries if desired, to obtain tablets or dragee cores. Suitable excipients include, but are not limited to, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose compositions such as maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carbomethylcellulose; and/or physiologically acceptable polymers such as polyvinylpyrrolidone (PVP) or polyethylene glycol (PEG). Disintegrating agents may also be added, such as cross-linked polyvinylpyrrolidone, agar, alginic acid or a salt thereof such as sodium alginate.

[0471] Tablets or capsules can be prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g., pregelatinized maize starch, polyvinylpyrrolidone, hydroxypropyl methylcellulose, carboxymethylcellulose, polyethylene glycol, sucrose, glucose, sorbitol, starch, gum, kaolin, and tragacanth); fillers (e.g., lactose, microcrystalline cellulose, or calcium hydrogen phosphate); lubricants (e.g., calcium, aluminum, zinc, stearic acid, polyethylene glycol, sodium lauryl sulfate, starch, sodium benzoate, L-leucine, magnesium stearate, talc, or silica); disintegrants (e.g., starch, potato starch, sodium starch glycolate, sugars, cellulose derivatives, silica powders); or wetting agents (e.g., sodium lauryl sulphate). The tablets may be coated by methods well known in the art. A coating shell may be present, and common membranes include, but are not limited to, polylactide, polyglycolic acid, polyanhydride, other biodegradable polymers, alginate-polylysine-alginate (APA), alginate-polymethylene-co-guanidine-alginate (A-PMCG-A), hydroymethylacrylate-methyl methacrylate (HEMA-MMA), multilayered HEMA-MMA-MAA, polyacrylonitrilevinylchloride (PAN-PVC), acrylonitrile/sodium methallylsulfonate (AN-69), polyethylene glycol/poly pentamethylcyclopentasiloxane/polydimethylsiloxane (PEG/PD5/PDMS), poly N,N-dimethyl acrylamide (PDMAAm), siliceous encapsulates, cellulose sulphate/sodium alginate/polymethylene-co-guanidine (CS/A/PMCG), cellulose acetate phthalate, calcium alginate, k-carrageenan-locust bean gum gel beads, gellan-xanthan beads, poly(lactide-co-glycolides), carrageenan, starch poly-anhydrides, starch polymethacrylates, polyamino acids, and enteric coating polymers.

[0472] In some embodiments, the genetically engineered bacteria are enterically coated for release into the gut or a particular region of the gut, for example, the large intestine. The typical pH profile from the stomach to the colon is about 1-4 (stomach), 5.5-6 (duodenum), 7.3-8.0 (ileum), and 5.5-6.5 (colon). In some diseases, the pH profile may be modified. In some embodiments, the coating is degraded in specific pH environments in order to specify the site of release. In some embodiments, at least two coatings are used. In some embodiments, the outside coating and the inside coating are degraded at different pH levels.

[0473] In some embodiments, enteric coating materials may be used, in one or more coating layers (e.g., outer, inner and/o intermediate coating layers). Enteric coated polymers remain unionized at low pH, and therefore remain insoluble. But as the pH increases in the gastrointestinal tract, the acidic functional groups are capable of ionization, and the polymer swells or becomes soluble in the intestinal fluid.

[0474] Materials used for enteric coatings include Cellulose acetate phthalate (CAP), Poly(methacrylic acid-co-methyl methacrylate), Cellulose acetate trimellitate (CAT), Poly(vinyl acetate phthalate) (PVAP) and Hydroxypropyl methylcellulose phthalate (HPMCP), fatty acids, waxes, Shellac (esters of aleurtic acid), plastics and plant fibers. Additionally, Zein, Aqua-Zein (an aqueous zein formulation containing no alcohol), amylose starch and starch derivatives, and dextrins (e.g., maltodextrin) are also used. Other known enteric coatings include ethylcellulose, methylcellulose, hydroxypropyl methylcellulose, amylose acetate phthalate, cellulose acetate phthalate, hydroxyl propyl methyl cellulose phthalate, an ethylacrylate, and a methylmethacrylate.

[0475] Coating polymers also may comprise one or more of, phthalate derivatives, CAT, HPMCAS, polyacrylic acid derivatives, copolymers comprising acrylic acid and at least one acrylic acid ester, Eudragit.TM. S (poly(methacrylic acid, methyl methacrylate)1:2); Eudragit L100.TM. S (poly(methacrylic acid, methyl methacrylate)1:1); Eudragit L30D.TM., (poly(methacrylic acid, ethyl acrylate)1:1); and (Eudragit L100-55) (poly(methacrylic acid, ethyl acrylate)1:1) (Eudragit.TM. L is an anionic polymer synthesized from methacrylic acid and methacrylic acid methyl ester), polymethyl methacrylate blended with acrylic acid and acrylic ester copolymers, alginic acid, ammonia alginate, sodium, potassium, magnesium or calcium alginate, vinyl acetate copolymers, polyvinyl acetate 30D (30% dispersion in water), a neutral methacrylic ester comprising poly(dimethylaminoethylacrylate) ("Eudragit E.TM.), a copolymer of methylmethacrylate and ethylacrylate with trimethylammonioethyl methacrylate chloride, a copolymer of methylmethacrylate and ethylacrylate, Zein, shellac, gums, or polysaccharides, or a combination thereof.

[0476] Coating layers may also include polymers which contain Hydroxypropylmethylcellulose (HPMC), Hydroxypropylethylcellulose (HPEC), Hydroxypropylcellulose (HPC), hydroxypropylethylcellulose (HPEC), hydroxymethylpropylcellulose (HMPC), ethylhydroxyethylcellulose (EHEC) (Ethulose), hydroxyethylmethylcellulose (HEMC), hydroxymethylethylcellulose (HMEC), propylhydroxyethylcellulose (PHEC), methylhydroxyethylcellulose (M H EC), hydrophobically modified hydroxyethylcellulose (NEXTON), carboxymethyl hydroxyethylcellulose (CMHEC), Methylcellulose, Ethylcellulose, water soluble vinyl acetate copolymers, gums, polysaccharides such as alginic acid and alginates such as ammonia alginate, sodium alginate, potassium alginate, acid phthalate of carbohydrates, amylose acetate phthalate, cellulose acetate phthalate (CAP), cellulose ester phthalates, cellulose ether phthalates, hydroxypropylcellulose phthalate (HPCP), hydroxypropylethylcellulose phthalate (HPECP), hydroxyproplymethylcellulose phthalate (HPMCP), hydroxyproplymethylcellulose acetate succinate (HPMCAS).

[0477] In some embodiments, the genetically engineered microorganisms are enterically coated for release into the gut or a particular region of the gut, for example, the large intestine. The typical pH profile from the stomach to the colon is about 1-4 (stomach), 5.5-6 (duodenum), 7.3-8.0 (ileum), and 5.5-6.5 (colon). In some diseases, the pH profile may be modified. In some embodiments, the coating is degraded in specific pH environments in order to specify the site of release. In some embodiments, at least two coatings are used. In some embodiments, the outside coating and the inside coating are degraded at different pH levels.

[0478] Liquid preparations for oral administration may take the form of solutions, syrups, suspensions, or a dry product for constitution with water or other suitable vehicle before use. Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable agents such as suspending agents (e.g., sorbitol syrup, cellulose derivatives, or hydrogenated edible fats); emulsifying agents (e.g., lecithin or acacia); non-aqueous vehicles (e.g., almond oil, oily esters, ethyl alcohol, or fractionated vegetable oils); and preservatives (e.g., methyl or propyl-p-hydroxybenzoates or sorbic acid). The preparations may also contain buffer salts, flavoring, coloring, and sweetening agents as appropriate. Preparations for oral administration may be suitably formulated for slow release, controlled release, or sustained release of the genetically engineered microorganisms described herein.

[0479] In one embodiment, the genetically engineered microorganisms of the disclosure may be formulated in a composition suitable for administration to pediatric subjects. As is well known in the art, children differ from adults in many aspects, including different rates of gastric emptying, pH, gastrointestinal permeability, etc. (Ivanovska et al., Pediatrics, 134(2):361-372, 2014). Moreover, pediatric formulation acceptability and preferences, such as route of administration and taste attributes, are critical for achieving acceptable pediatric compliance. Thus, in one embodiment, the composition suitable for administration to pediatric subjects may include easy-to-swallow or dissolvable dosage forms, or more palatable compositions, such as compositions with added flavors, sweeteners, or taste blockers. In one embodiment, a composition suitable for administration to pediatric subjects may also be suitable for administration to adults.

[0480] In one embodiment, the composition suitable for administration to pediatric subjects may include a solution, syrup, suspension, elixir, powder for reconstitution as suspension or solution, dispersible/effervescent tablet, chewable tablet, gummy candy, lollipop, freezer pop, troche, chewing gum, oral thin strip, orally disintegrating tablet, sachet, soft gelatin capsule, sprinkle oral powder, or granules. In one embodiment, the composition is a gummy candy, which is made from a gelatin base, giving the candy elasticity, desired chewy consistency, and longer shelf-life. In some embodiments, the gummy candy may also comprise sweeteners or flavors.

[0481] In one embodiment, the composition suitable for administration to pediatric subjects may include a flavor. As used herein, "flavor" is a substance (liquid or solid) that provides a distinct taste and aroma to the formulation. Flavors also help to improve the palatability of the formulation. Flavors include, but are not limited to, strawberry, vanilla, lemon, grape, bubble gum, and cherry.

[0482] In certain embodiments, the genetically engineered microorganisms may be orally administered, for example, with an inert diluent or an assimilable edible carrier. The compound may also be enclosed in a hard or soft shell gelatin capsule, compressed into tablets, or incorporated directly into the subject's diet. For oral therapeutic administration, the compounds may be incorporated with excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and the like. To administer a compound by other than parenteral administration, it may be necessary to coat the compound with, or co-administer the compound with, a material to prevent its inactivation.

[0483] In another embodiment, the pharmaceutical composition comprising the recombinant bacteria of the invention may be a comestible product, for example, a food product. In one embodiment, the food product is milk, concentrated milk, fermented milk (yogurt, sour milk, frozen yogurt, lactic acid bacteria-fermented beverages), milk powder, ice cream, cream cheeses, dry cheeses, soybean milk, fermented soybean milk, vegetable-fruit juices, fruit juices, sports drinks, confectionery, candies, infant foods (such as infant cakes), nutritional food products, animal feeds, or dietary supplements. In one embodiment, the food product is a fermented food, such as a fermented dairy product. In one embodiment, the fermented dairy product is yogurt. In another embodiment, the fermented dairy product is cheese, milk, cream, ice cream, milk shake, or kefir. In another embodiment, the recombinant bacteria of the invention are combined in a preparation containing other live bacterial cells intended to serve as probiotics. In another embodiment, the food product is a beverage. In one embodiment, the beverage is a fruit juice-based beverage or a beverage containing plant or herbal extracts. In another embodiment, the food product is a jelly or a pudding. Other food products suitable for administration of the recombinant bacteria of the invention are well known in the art. For example, see U.S. 2015/0359894 and US 2015/0238545, the entire contents of each of which are expressly incorporated herein by reference. In yet another embodiment, the pharmaceutical composition of the invention is injected into, sprayed onto, or sprinkled onto a food product, such as bread, yogurt, or cheese.

[0484] In some embodiments, the composition is formulated for intraintestinal administration, intrajejunal administration, intraduodenal administration, intraileal administration, gastric shunt administration, or intracolic administration, via nanoparticles, nanocapsules, microcapsules, or microtablets, which are enterically coated or uncoated. The pharmaceutical compositions may also be formulated in rectal compositions such as suppositories or retention enemas, using, e.g., conventional suppository bases such as cocoa butter or other glycerides. The compositions may be suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain suspending, stabilizing and/or dispersing agents.

[0485] The genetically engineered microorganisms described herein may be administered intranasally, formulated in an aerosol form, spray, mist, or in the form of drops, and conveniently delivered in the form of an aerosol spray presentation from pressurized packs or a nebuliser, with the use of a suitable propellant (e.g., dichlorodifluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide or other suitable gas). Pressurized aerosol dosage units may be determined by providing a valve to deliver a metered amount. Capsules and cartridges (e.g., of gelatin) for use in an inhaler or insufflator may be formulated containing a powder mix of the compound and a suitable powder base such as lactose or starch.

[0486] The genetically engineered microorganisms may be administered and formulated as depot preparations. Such long acting formulations may be administered by implantation or by injection, including intravenous injection, subcutaneous injection, local injection, direct injection, or infusion. For example, the compositions may be formulated with suitable polymeric or hydrophobic materials (e.g., as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives (e.g., as a sparingly soluble salt).

[0487] In some embodiments, disclosed herein are pharmaceutically acceptable compositions in single dosage forms. Single dosage forms may be in a liquid or a solid form. Single dosage forms may be administered directly to a patient without modification or may be diluted or reconstituted prior to administration. In certain embodiments, a single dosage form may be administered in bolus form, e.g., single injection, single oral dose, including an oral dose that comprises multiple tablets, capsule, pills, etc. In alternate embodiments, a single dosage form may be administered over a period of time, e.g., by infusion.

[0488] Single dosage forms of the pharmaceutical composition may be prepared by portioning the pharmaceutical composition into smaller aliquots, single dose containers, single dose liquid forms, or single dose solid forms, such as tablets, granulates, nanoparticles, nanocapsules, microcapsules, microtablets, pellets, or powders, which may be enterically coated or uncoated. A single dose in a solid form may be reconstituted by adding liquid, typically sterile water or saline solution, prior to administration to a patient.

[0489] In other embodiments, the composition can be delivered in a controlled release or sustained release system. In one embodiment, a pump may be used to achieve controlled or sustained release. In another embodiment, polymeric materials can be used to achieve controlled or sustained release of the therapies of the present disclosure (see e.g., U.S. Pat. No. 5,989,463). Examples of polymers used in sustained release formulations include, but are not limited to, poly(2-hydroxy ethyl methacrylate), poly(methyl methacrylate), poly(acrylic acid), poly(ethylene-co-vinyl acetate), poly(methacrylic acid), polyglycolides (PLG), polyanhydrides, poly(N-vinyl pyrrolidone), poly(vinyl alcohol), polyacrylamide, poly(ethylene glycol), polylactides (PLA), poly(lactide-co-glycolides) (PLGA), and polyorthoesters. The polymer used in a sustained release formulation may be inert, free of leachable impurities, stable on storage, sterile, and biodegradable. In some embodiments, a controlled or sustained release system can be placed in proximity of the prophylactic or therapeutic target, thus requiring only a fraction of the systemic dose. Any suitable technique known to one of skill in the art may be used.

[0490] Dosage regimens may be adjusted to provide a therapeutic response. Dosing can depend on several factors, including severity and responsiveness of the disease, route of administration, time course of treatment (days to months to years), and time to amelioration of the disease. For example, a single bolus may be administered at one time, several divided doses may be administered over a predetermined period of time, or the dose may be reduced or increased as indicated by the therapeutic situation. The specification for the dosage is dictated by the unique characteristics of the active compound and the particular therapeutic effect to be achieved. Dosage values may vary with the type and severity of the condition to be alleviated. For any particular subject, specific dosage regimens may be adjusted over time according to the individual need and the professional judgment of the treating clinician. Toxicity and therapeutic efficacy of compounds provided herein can be determined by standard pharmaceutical procedures in cell culture or animal models. For example, LD.sub.50, ED.sub.50, EC.sub.50, and IC.sub.50 may be determined, and the dose ratio between toxic and therapeutic effects (LD.sub.50/ED.sub.50) may be calculated as the therapeutic index. Compositions that exhibit toxic side effects may be used, with careful modifications to minimize potential damage to reduce side effects. Dosing may be estimated initially from cell culture assays and animal models. The data obtained from in vitro and in vivo assays and animal studies can be used in formulating a range of dosage for use in humans.

[0491] The ingredients are supplied either separately or mixed together in unit dosage form, for example, as a dry lyophilized powder or water-free concentrate in a hermetically sealed container such as an ampoule or sachet indicating the quantity of active agent. If the mode of administration is by injection, an ampoule of sterile water for injection or saline can be provided so that the ingredients may be mixed prior to administration.

[0492] The pharmaceutical compositions may be packaged in a hermetically sealed container such as an ampoule or sachet indicating the quantity of the agent. In one embodiment, one or more of the pharmaceutical compositions is supplied as a dry sterilized lyophilized powder or water-free concentrate in a hermetically sealed container and can be reconstituted (e.g., with water or saline) to the appropriate concentration for administration to a subject. In an embodiment, one or more of the prophylactic or therapeutic agents or pharmaceutical compositions is supplied as a dry sterile lyophilized powder in a hermetically sealed container stored between 2.degree. C. and 8.degree. C. and administered within 1 hour, within 3 hours, within 5 hours, within 6 hours, within 12 hours, within 24 hours, within 48 hours, within 72 hours, or within one week after being reconstituted. Cryoprotectants can be included for a lyophilized dosage form, principally 0-10% sucrose (optimally 0.5-1.0%). Other suitable cryoprotectants include trehalose and lactose. Other suitable bulking agents include glycine and arginine, either of which can be included at a concentration of 0-0.05%, and polysorbate-80 (optimally included at a concentration of 0.005-0.01%). Additional surfactants include but are not limited to polysorbate 20 and BRIJ surfactants. The pharmaceutical composition may be prepared as an injectable solution and can further comprise an agent useful as an adjuvant, such as those used to increase absorption or dispersion, e.g., hyaluronidase.

[0493] In some embodiments, the genetically engineered microorganisms and composition thereof is formulated for intravenous administration, intratumor administration, or peritumor administration. The genetically engineered microorganisms may be formulated as depot preparations. Such long acting formulations may be administered by implantation or by injection. For example, the compositions may be formulated with suitable polymeric or hydrophobic materials (e.g., as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives (e.g., as a sparingly soluble salt).

[0494] In some embodiments, the genetically engineered OVs are prepared for delivery, taking into consideration the need for efficient delivery and for overcoming the host antiviral immune response. Approaches to evade antiviral response include the administration of different viral serotypes as part of the treatment regimen (serotype switching), formulation, such as polymer coating to mask the virus from antibody recognition and the use of cells as delivery vehicles.

[0495] In another embodiment, the composition can be delivered in a controlled release or sustained release system. In one embodiment, a pump may be used to achieve controlled or sustained release. In another embodiment, polymeric materials can be used to achieve controlled or sustained release of the therapies of the present disclosure (see e.g., U.S. Pat. No. 5,989,463). Examples of polymers used in sustained release formulations include, but are not limited to, poly(2-hydroxy ethyl methacrylate), poly(methyl methacrylate), poly(acrylic acid), poly(ethylene-co-vinyl acetate), poly(methacrylic acid), polyglycolides (PLG), polyanhydrides, poly(N-vinyl pyrrolidone), poly(vinyl alcohol), polyacrylamide, poly(ethylene glycol), polylactides (PLA), poly(lactide-co-glycolides) (PLGA), and polyorthoesters. The polymer used in a sustained release formulation may be inert, free of leachable impurities, stable on storage, sterile, and biodegradable. In some embodiments, a controlled or sustained release system can be placed in proximity of the prophylactic or therapeutic target, thus requiring only a fraction of the systemic dose. Any suitable technique known to one of skill in the art may be used.

[0496] The genetically engineered bacteria of the invention may be administered and formulated as neutral or salt forms. Pharmaceutically acceptable salts include those formed with anions such as those derived from hydrochloric, phosphoric, acetic, oxalic, tartaric acids, etc., and those formed with cations such as those derived from sodium, potassium, ammonium, calcium, ferric hydroxides, isopropylamine, triethylamine, 2-ethylamino ethanol, histidine, procaine, etc.

Methods of Treatment

[0497] Another aspect provides methods of treating microbial infections, e.g., COVID-19. In some embodiments, the invention provides methods for reducing, ameliorating, or eliminating one or more symptom(s) associated with COVID-19. In some embodiments, the symptom(s) associated thereof include, but are not limited to, runny nose, sneezing, headache, cough, sore throat, fever, or short of breath. In more severe cases, coronavirus infection can cause pneumonia, severe acute respiratory syndrome, kidney failure and even death.

[0498] The method may comprise preparing a pharmaceutical composition with at least one genetically engineered species, strain, or subtype of bacteria described herein, and administering the pharmaceutical composition to a subject in a therapeutically effective amount. The genetically engineered microorganisms may be administered intravenously, intranasally, intra-arterially, intramuscularly, intraperitoneally, orally, or topically. In some embodiments, the genetically engineered microorganisms are administered intravenously, i.e., systemically.

[0499] In certain embodiments, administering the pharmaceutical composition to the subject reduces viral infection in a subject. In some embodiments, the methods of the present disclosure may reduce viral infection by at least about 10% to 20%, 20% to 25%, 25% to 30%, 30% to 40%, 40% to 50%, 50% to 60%, 60% to 70%, 70% to 75%, 75% to 80%, 80% to 85%, 85% to 90%, 90% to 95%, 95% to 99%, or more as compared to levels in an untreated or control subject.

[0500] For genetically engineered microorganisms expressing immune-based immune modulators, responses patterns may be different than for traditional cytotoxic therapies. Thus, the pharmaceutical composition comprising the gene or gene cassette for producing the immune modulator may be re-administered at a therapeutically effective dose and frequency. In alternate embodiments, the genetically engineered bacteria are not destroyed within hours or days after administration and may propagate in the target site.

[0501] The pharmaceutical composition may be administered alone or in combination with one or more additional therapeutic agents, e.g., as described herein and known in the art. An important consideration in selecting the one or more additional therapeutic agents is that the agent(s) should be compatible with the genetically engineered bacteria of the invention, e.g., the agent(s) must not kill the bacteria.

[0502] In certain embodiments, the pharmaceutical composition may be administered to a subject by administering a first genetically engineered bacterium to the subject, wherein the first genetically engineered bacterium comprises at least one gene encoding a first immune initiator; and administering a second genetically engineered bacterium to the subject, wherein the second genetically engineered bacterium comprising at least one gene encoding a second immune initiator. In some embodiments, the administering steps are performed at the same time. In some embodiments, administering the first genetically engineered bacterium to the subject occurs before the administering of the second genetically engineered bacterium to the subject. In some embodiments, administering of the second genetically engineered bacterium to the subject occurs before the administering of the first genetically engineered bacterium to the subject. In some embodiments, the ratio of the first genetically engineered bacterium to the second genetically engineered bacterium is 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, or 1:5. In some embodiments, the ratio of the second genetically engineered bacterium to the first genetically engineered bacterium is 5:1, 4:1, 3:1, 2:1, 1:1, 1:2, 1:3, 1:4, or 1:5.

Treatment In Vivo

[0503] The modified microorganisms may be evaluated in vivo, e.g., in an animal model. Any suitable animal model of a disease or condition associated with COVID-19 may be used. The genetically engineered bacteria may be administered to the animal systemically or locally, e.g., via oral administration (gavage), intravenous, or subcutaneous injection or via intranasal injection, and treatment efficacy determined.

EXAMPLES

[0504] The following examples provide illustrative embodiments of the disclosure. One of ordinary skill in the art will recognize the numerous modifications and variations that may be performed without altering the spirit or scope of the disclosure. Such modifications and variations are encompassed within the scope of the disclosure. The Examples do not in any way limit the disclosure.

[0505] The disclosure provides herein a sequence having at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% homologous to the sequence any of the SEQ ID NOs described in the Examples, below.

Example 1. Development of a Recombinant Bacteria for Surface Display of Proteins

[0506] Microbial infection can be caused by bacteria, fungi, and viruses. A vaccine for the prevention and/or treatment of a bacterial, viral, or fungal infection is developed by utilizing synthetic biology techniques to engineer probiotic bacteria that express one or more proteins (e.g., viral, bacterial, fungal, and cancer) and immune activators/adjuvants. This vaccine is based on an engineered E. coli Nissle (EcN) bacterial strain that expresses one or more proteins (e.g., viral, bacterial, fungal, and cancer) and can be administered, e.g., intranasally, to induce protective immunity systemically and/or at mucosal surfaces.

[0507] Engineered E. coli Nissle cells are designed to display one or more proteins (e.g., viral, bacterial, fungal, and cancer) and immune activators/adjuvants on the Nissle membrane. The proteins and immune activators/adjuvants are expressed as fusion proteins referred to herein as "display proteins" comprising an anchor domain(s), a linker, and a displayed protein(s). In some embodiments, the displayed protein is a reporter protein, e.g., GFP (FIG. 1).

[0508] To begin with, to create an E. coli Nissle derivative capable of secreting bioactive proteins, a engineered a diffusible outer membrane (DOM) phenotype was generated by deleting the gene encoding the periplasmic protein peptidoglycan associated lipoprotein (PAL, MQLNKVLKGLMIALPVMAIAACSSNKNASNDGSEGMLGAGTGMDANGGNGNMSSEEQAR LQMQQLQQNNIVYFDLDKYDIRSDFAQMLDAHANFLRSNPSYKVTVEGHADERGTPEYNIS LGERRANAVKMYLQGKGVSADQISIVSYGKEKPAVLGHDEAAYAKNRRAVLVY (SEQ ID NO: 1483). This alteration results in an increased rate of diffusion of periplasmic proteins to the external environment without compromising cell growth properties. The resulting `leaky` chassis strain is designated SYN1557 (Nissle delta PAL::CmR).

[0509] E. coli Nissle cells were further designed to express fusion proteins including an anchor domain, an AB epitope (e.g., FLAG tag), and a displayed reporter, e.g., GFP. Constructs were transformed into SYN1557 (deltaPAL, diffusible outer membrane (DOM) phenotype). As shown in FIG. 2, GFP and FLAG tag were displayed when combined with three different anchor domains and analyzed by flow cytometry. Briefly, a bacterial culture expressing either a negative control construct or surface display construct was centrifuged and the pellet was washed in PBS. The bacterial pellet was resuspended in PBS and antibody was added (e.g., anti-GFP and anti-FLAG). The mixture was incubated at room temperature for 30 minutes. After incubation, the cell and antibody mixture was centrifuged and the resulting cell pellet was resuspended in PBS. Centrifugation and resuspension of the cell pellet was repeated. The resulting cell pellet was resuspended in PBS and the cell suspension was analyzed by flow cytometry. Macquant VYB flow cytometer was used to analyze the samples and collected the data. The data were analyzed using Macsquantify software provided by Miltenyi. FSC=580V, SSC=340V, Y2 (red)=820V, B1 (green)=660V. The FSC and SSC were set up specifically for the visualization of E. coli Nissle. The gating strategy was set up facilitated by negative control and E. coli Nissle strain.

[0510] GFP was displayed when using constructs containing InvasionN, YiaT, or IntiminT as the anchor domain (FIG. 3). The constructs are shown in Table 7 below.

TABLE-US-00007 TABLE 7 Strains for GFP display (FIG. 3) Strain Number Construct SYN1557 E. coli Nissle delta PAL:CmR SYN6819 p15A-invasinN-FLAG-GFP-HIS SYN6820 p15A-yiaT-FLAG-GFP-HIS SYN6821 p15A-intiminN-FLAG-GFP-HIS

[0511] GFP was displayed when using constructs containing pelB-PAL, BAN, LppOmpA, NGIgAsig, or OsmY as the anchor domain (FIGS. 4A and 4B). The constructs are shown in Table 8 below. Construct sequences are shown in Tables 10 and 11 below. Amino acid sequences are shown in Table 12.

TABLE-US-00008 TABLE 8 Strains for GFP display (FIGs. 4A and 4B) Strain Number Construct SYN1557 E. coli Nissle delta PAL:CmR SYN5984 p15A-Kan-ptet-pelB-FLAG-dasherGFP-HIS-PAL SYN5986 p15A-Kan-ptet-BAN-FLAG-GFP-HIS SYN5987 p15A-Kan-ptet-FLAG-GFP-HIS SYN5988 p15A-Kan-ptet-LppOmpA-FLAG-GFP-HIS SYN5989 p15A-Kan-ptet-NGIgAsig-FLAG-GFP-HIS-NGIgAb SYN6068 p15A-Kan-ptet-pelB-FLAG-dasherGFP-HIS SYN6070 p15A-Kan-ptet-FLAG-GFP-HIS-OsmY

[0512] GFP was displayed when using constructs containing pelB-PAL, BAN, LppOmpA, NGIgAsig, or OsmY as the anchor domain (FIGS. 5A-5C). The constructs are shown in Table 9 below. Construct DNA sequences are shown in Tables 10 and 11 below. Amino acid sequences are shown in Table 12.

TABLE-US-00009 TABLE 9 Strains for GFP display (FIGs. 5A-5C) Strain Number Construct SYN094 SYN2612 p15A-Kan-ptet-pelB-FLAG-dasherGFP-HIS-PAL SYN5985 p15A-Kan-ptet-BAN-FLAG-GFP-HIS SYN2609 p15A-Kan-ptet-FLAG-GFP-HIS SYN2610 p15A-Kan-ptet-LppOmpA-FLAG-GFP-HIS SYN2611 p15A-Kan-ptet-NGIgAsig-FLAG-GFP-HIS-NGIgAb SYN6067 p15A-Kan-ptet-pelB-FLAG-dasherGFP-HIS SYN6069 p15A-Kan-ptet-FLAG-GFP-HIS-OsmY

TABLE-US-00010 TABLE 10 Construct DNA Sequences Construct DNA sequence p15A-Kan- tagcggagtgtatactggcttactatgttggca ptet-pelB- ctgatgagggtgtcagtgaagtgcttcatgtgg FLAG- caggagaaaaaaggctgcaccggtgcgtcagca dasherGFP- gaatatgtgatacaggatatattccgcttcctc HIS- gctcactgactcgctacgctcggtcgttcgact PAL gcggcgagcggaaatggcttacgaacggggcgg agatttcctggaagatgccaggaagatacttaa cagggaagtgagagggccgcggcaaagccgttt ttccataggctccgcccccctgacaagcatcac gaaatctgacgctcaaatcagtggtggcgaaac ccgacaggactataaagataccaggcgtttccc ctggcggctccctcgtgcgctctcctgttcctg cctttcggtttaccggtgtcattccgctgttat ggccgcgtttgtctcattccacgcctgacactc agttccgggtaggcagttcgctccaagctggac tgtatgcacgaaccccccgttcagtccgaccgc tgcgccttatccggtaactatcgtcttgagtcc aacccggaaagacatgcaaaagcaccactggca gcagccactggtaattgatttagaggagttagt cttgaagtcatgcgccggttaaggctaaactga aaggacaagttttggtgactgcgctcctccaag ccagttacctcggttcaaagagttggtagctca gagaaccttcgaaaaaccgccctgcaaggcggt tttttcgttttcagagcaagagattacgcgcag accaaaacgatctcaagaagatcatcttattaa ggggtctgacgctcagtggaacggtgcaccctg cagggctagctgataaagcgttcgcgctgcatt cggcagtttaagacccactttcacatttaagtt gtttttctaatccgcatatgatcaattcaaggc cgaataagaaggctggctctgcaccttggtgat caaataattcgatagcttgtcgtaataatggcg gcatactatcagtagtaggtgtttccctttctt ctttagcgacttgatgctcttgatcttccaata cgcaacctaaagtaaaatgccccacagcgctga gtgcatataatgcattctctagtgaaaaacctt gttggcataaaaaggctaattgattttcgagag tttcatactgtttttctgtaggccgtgtaccta aatgtacttttgctccatcgcgatgacttagta aagcacatctaaaacttttagcgttattacgta aaaaatcttgccagctttccccttctaaagggc aaaagtgagtatggtgcctatctaacatctcaa tggctaaggcgtcgagcaaagcccgcttatttt ttacatgccaatacaatgtaggctgctctacac ctagcttctgggcgagtttacgggttgttaaac cttcgattccgacctcattaagcagctctaatg cgctgttaatcactttacttttatctaatctag acatcattaattcctaatttttgttgacactct atcattgatagagttattttaccactccctatc agtgatagagaaaagtgaaaggaggtaaattAT GAAATATCTTCTTCCAACGGCTGCTGCTGGTTT ATTGCTTCTTGCCGCCCAGCCTGCGATGGCTAC TAGTGAGTATAAGGATGACGACGACAAGagatc tacggcattgacggaaggtgcaaaactgtttga gaaagagatcccgtatatcaccgaactggaagg cgacgtcgaaggtatgaaatttatcattaaagg cgagggtaccggtgacgcgaccacgggtaccat taaagcgaaatacatctgcactacgggcgacct gccggtcccgtgggcaaccctggtgagcaccct gagctacggtgttcagtgtttcgccaagtaccc gagccacatcaaggatttctttaagagcgccat gccggaaggttatacccaagagcgtaccatcag cttcgaaggcgacggcgtgtacaagacgcgtgc tatggttacctacgaacgcggttctatctacaa tcgtgtcacgctgactggtgagaactttaagaa agacggtcacattctgcgtaagaacgttgcatt ccaatgcccgccaagcattctgtatattctgcc tgacaccgttaacaatggcatccgcgttgagtt caaccaggcgtacgatattgaaggtgtgaccga aaaactggttaccaaatgcagccaaatgaatcg tccgttggcgggctccgcggcagtgcatatccc gcgttatcatcacattacctaccacaccaaact gagcaaagaccgcgacgagcgccgtgatcacat gtgtctggtagaggtcgtgaaagcggttgatct ggacacgtatcagGGATCCGGCCACCACCATCA TCACCACTGCAGTAGCAATAAAAATGCTTCGAA TGACGGATCGGAAGGAATGTTAGGTGCTGGTAC TGGCATGGACGCCAACGGTGGCAACGGAAATAT GTCTAGCGAAGAACAAGCTCGTTTAGAAATGCA GCAATTACAGCAAAACAACATAGTCTACTTCGA CTTAGACAAGTACGACATCCGTAGCGATTTTGC ACAAATGTTGGATGCCCATGCCAACTTCCTTCG TTCTAATCCAAGCTACAAAGTCACTGTTGAGGG CCACGCGGATGAGAGAGGCACTCCTGAATATAA CATATCCCTGGGGGAGCGCAGAGCAAACGCCGT AAAAATGTACCTGCAAGGCAAGGGCGTCTCGGC CGATCAAATCTCGATCGTGAGCTATGGCAAAGA GAAACCGGCTGTATTGGGACATGACGAAGCTGC TTACAGCAAGAATCGGCGGGCCGTCTTGGTCTA CtaataaGCATGCTAATCAGCCGTGGAATTCGC AACGTAAAAAAACCCGCCCCGGCGGGTTTTTTT ATAGCGGTCTCaGGAGgAACGATTGGTAAAGCC GGTGaacgcatgagAAAGCGCGCGGAAGATCAC GTTCCGGGGGCTTTtttattgcgcGGACCAAAA CGAAAAAAGACGCTCGAAAGCGTCTCTTTTCTG GAATTTaaatgaaactgcaatttattcatatca ggattatcaataccatatttttgaaaaagccgt ttctgtaatgaaggagaaaactcaccgaggcag ttccataggatggcaagatcctggtatcggtct gcgattccgactcgtccaacatcaatacaacct attaatttcccctcgtcaaaaataaggttatca agtgagaaatcaccatgagtgacgactgaatcc ggtgagaatggcaaaagcttatgcatttctttc cagacttgttcaacaggccagccattacgctcg tcatcaaaatcactcgcatcaaccaaaccgtta ttcattcgtgattgcgcctgagcgagacgaaat acgcgatcgctgttaaaaggacaattacaaaca ggaatcgaatgcaaccggcgcaggaacactgcc agcgcatcaacaatattttcacctgaatcagga tattcttctaatacctggaatgctgttttcccg gggatcgcagtggtgagtaaccatgcatcatca ggagtacggataaaatgcttgatggtcggaaga ggcataaattccgtcagccagtttagtctgacc atctcatctgtaacatcattggcaacgctacct ttgccatgtttcagaaacaactctggcgcatcg ggcttcccatacaatcgatagattgtcgcacct gattgcccgacattatcgcgagcccatttatac ccatataaatcagcatccatgttggaatttaat cgcggcctcgagcaagacgtttcccgttgaata tggctcataacaccccttgtattactgtttatg taagcagacagttttattgttcatgatgatata tttttatcttgtgcaatgtaacatcagagattt tgagacacaacgtggctttgttgaataaatcga acttttgctgagttgaaggatcagatcacgcat cttcccgacaacgcagaccgttccgtggcaaag caaaagttcaaaatcaccaactggtccacctac aacaaagctctcatcaaccgtggctccctcact ttctggctggatgatggggcgattcaggcctgg tatgagtcagcaacaccttcttcacgaggcaga cctcagcgc (SEQ ID NO: 1484) p15A-Kan- tagcggagtgtatactggcttactatgttggca ptet- ctgatgagggtgtcagtgaagtgcttcatgtgg BAN-FLAG- caggagaaaaaaggctgcaccggtgcgtcagca GFP-HIS gaatatgtgatacaggatatatKcgcttcctcg ctcactgactcgctacgctcggtcgttcgactg cggcgagcggaaatggcttacgaacggggcgga gatttcctggaagatgccaggaagatacttaac agggaagtgagagggccgcggcaaagccgtttt tccataggctccgcccccctgacaagcatcacg aaatctgacgctcaaatcagtggtggcgaaacc cgacaggactataaagataccaggcgtttcccc tggcggctccctcgtgcgctctcctgttcctgc ctttcggtttaccggtgtcattccgctgttatg gccgcgtttgtctcattccacgcctgacactca gttccgggtaggcagttcgctccaagctggact gtatgcacgaaccccccgttcagtccgaccgct gcgccttatccggtaactatcgtcttgagtcca acccggaaagacatgcaaaagcaccactggcag cagccactggtaattgatttagaggagttagtc ttgaagtcatgcgccggttaaggctaaactgaa aggacaagttttggtgactgcgctcctccaagc cagttacctcggttcaaagagttggtagctcag agaaccttcgaaaaaccgccctgcaaggcggtt ttttcgttttcagagcaagagattacgcgcaga ccaaaacgatctcaagaagatcatcttattaag gggtctgacgctcagtggaacggtgcaccctgc agggctagctgataaagcgttcgcgctgcattc ggcagtttaagacccactttcacatttaagttg ttmctaatccgcatatgatcaattcaaggccga ataagaaggctggctctgcaccttggtgatcaa ataattcgatagcttgtcgtaataatggcggca tactatcagtagtaggtgtttccctttcttctt tagcgacttgatgctcttgatcttccaatacgc aacctaaagtaaaatgccccacagcgctgagtg catataatgcattctctagtgaaaaaccttgtt ggcataaaaaggctaattgattttcgagagttt catactgtttttctgtaggccgtgtacctaaat gtacttttgctccatcgcgatgacttagtaaag cacatctaaaacttttagcgttattacgtaaaa aatcttgccagctttccccttctaaagggcaaa agtgagtatggtgcctatctaacatctcaatgg ctaaggcgtcgagcaaagcccgcttatttttta catgccaatacaatgtaggctgctctacaccta gcttctgggcgagtttacgggttgttaaacctt cgattccgacctcattaagcagctctaatgcgc tgttaatcactttacttttatctaatctagaca tcattaattcctaatttttgttgacactctatc attgatagagttattttaccactccctatagtg atagagaaaagtgaaaggaggtaaattATGACT AGTGCTTTTGACCCCAATCTGGTTGGGCCTACG TTACCTCCAATTCCGCCTTTCACTCTGCCTACG GACTATAAGGATGACGACGACAAGagatctacg gcattgacggaaggtgcaaaactgtttgagaaa gagatcccgtatatcaccgaactggaaggcgac gtcgaaggtatgaaatttatcattaaaggcgag ggtaccggtgacgcgaccacgggtaccattaaa gcgaaatacatctgcactacgggcgacctgccg gtcccgtgggcaaccctggtgagcaccctgagc tacggtgttcagtgtttcgccaagtacccgagc cacatcaaggatttctttaagagcgccatgccg gaaggttatacccaagagcgtaccatcagcttc gaaggcgacggcgtgtacaagacgcgtgctatg gttacctacgaacgcggttctatctacaatcgt gtcacgctgactggtgagaactttaagaaagac ggtcacattctgcgtaagaacgttgcattccaa tgcccgccaagcattctgtatattctgcctgac accgttaacaatggcatccgcgttgagttcaac caggcgtacgatattgaaggtgtgaccgaaaaa ctggttaccaaatgcagccaaatgaatcgtccg ttggcgggctccgcggcagtgcatatcccgcgt tatcatcacattacctaccacaccaaactgagc aaagaccgcgacgagcgccgtgatcacatgtgt ctggtagaggtcgtgaaagcggttgatctggac acgtatcagGGATCCGGCCACCACCATCATCAC CACtaataaGCATGCTAATCAGCCGTGGAATTC GGTCTCaGGAGgAACGATTGGTAAACCCGGTGa acgcatgagAAAGCCCCCGGAAGATCACCTTCC GGGGGCTTTtttattgcgcGGACCAAAACGAAA AAAGACGCTCGAAAGCGTCTCTTTTCTGGAATT TGGTACCGAGGcgtaatgctctgccagtgttac aaccaattaaccaattctgattagaaaaactca tcgagcatcaaatgaaactgcaatttattcata tcaggattatcaataccatatttttgaaaaagc cgtttctgtaatgaaggagaaaactcaccgagg cagttccataggatggcaagatcctggtatcgg tctgcgattccgactcgtccaacatcaatacaa cctattaatttcccctcgtcaaaaataaggtta tcaagtgagaaatcaccatgagtgacgactgaa tccggtgagaatggcaaaagcttatgcatttct ttccagacttgttcaacaggccagccattacgc tcgtcatcaaaatcactcgcatcaaccaaaccg ttattcattcgtgattgcgcctgagcgagacga aatacgcgatcgctgttaaaaggacaattacaa acaggaatcgaatgcaaccggcgcaggaacact gccagcgcatcaacaatattttcacctgaatca ggatattcttctaatacctggaatgctgttttc ccggggatcgcagtggtgagtaaccatgcatca tcaggagtacggataaaatgcttgatggtcgga agaggcataaattccgtcagccagtttactctg accatctcatctgtaacatcattggcaacgcta cctttgccatgtttcagaaacaactctggcgca tcgggcttcccatacaatcgatagattgtcgca cctgattgcccgacattatcgcgagcccattta tacccatataaatcagcatccatgttggaattt aatcgcggcctcgagcaagacgtttcccgttga atatggctcataacaccccttgtattactgttt atgtaagcagacagttttattgttcatgatgat atatttttatcttgtgcaatgtaacatcagaga ttttgagacacaacgtggctttgttgaataaat cgaacttttgctgagttgaaggatcagatcacg catcttcccgacaacgcagaccgttccgtggca aagcaaaagttcaaaatcaccaactggtccacc tacaacaaagctctcatcaaccgtggctccctc actttctggctggatgatggggcgattcaggcc tggtatgagtcagcaacaccttcttcacgaggc

agacctcagcgc (SEQ ID NO: 1485) p15A-Kan- tggcataaaaaggctaattgattttcgagagtt ptet- tcatactgtttttctgtaggccgtgtacctaaa LppOmpA- tgtacttttgctccatcgcgatgacttagtaaa FLAG-GFP- gcacatctaaaacttttagcgttattacgtaaa HIS aaatcttgccagctttccccttctaaagggcaa aagtgagtatggtgcctatctaacatctcaatg gctaaggcgtcgagcaaagcccgcttatttttt acatgccaatacaatgtaggctgctctacacct agcttctgggcgagtttacgggttgttaaacct tcgattccgacctcattaagcagctctaatgcg ctgttaatcactttacttttatctaatctagac atcattaattcctaatttttgttgacactctat cattgatagagttattttaccactccctatcag tgatagagaaaagtgaaaggaggtaaattATGA CTAGTAAAGCAACAAAACTTGTGTTAGGCGCGG TTATACTTGGCTCCACCCTGCTTGCAGGTTGCT CGTCTAACGCGAAGATCGACCAGGGTATCAATC CTTACGTCGGGTTTGAAATGGGATACGATTGGT TGGGACGTATGCCTTATAAGGGAAGTGTTGAAA ACGGCGCTTATAAGGCGCAGGGAGTACAGTTAA CGGCCAAGCTTGGGTACCCCATAACAGACGATT TAGATATTTATACCCGTTTAGGAGGAATGGTTT GGAGAGCCGACACGAAGTCTAATGTATATGGTA AGAACCACGACACGGGAGTATCCCCCGTCTTTG CAGGGGGAGTGGAATATGCTATCACACCAGAGA TCGCTACCCGTITGGAATATCAATGGACGAATA ATATAGGCGACGCCCATACGATAGGAACGCGGC CCGACAACGGCATCCCTGGGGTcGACTATAAGG ATGACGACGACAAGcaattgacggcattgacgg aaggtgcaaaactgtttgagaaagagatcccgt atatcaccgaactggaaggcgacgtcgaaggta tgaaatttatcattaaaggcgagggtaccggtg acgcgaccacgggtaccattaaagcgaaataca tctgcactacgggcgacctgccggtcccgtggg caaccctggtgagcaccctgagctacggtgttc agtgtttcgccaagtacccgagccacatcaagg atttctttaagagcgccatgccggaaggttata cccaagagcgtaccatcagcttcgaaggcgacg gcgtgtacaagacgcgtgctatggttacctacg aacgcggttctatctacaatcgtgtcacgctga ctggtgagaactttaagaaagacggtcacattc tgcgtaagaacgttgcattccaatgcccgccaa gcatttctgtatattctgcctgacaccgttaac aattggcatccgcgttgagttcaaccaggcgta cgatattgaaggtgtgaccgaaaaactggttac caaatgcagccaaatgaatcgtccgttggcggg ctccgcggcagtgcatatcccgcgttatcatca cattacctaccacaccaaactgagcaaagaccg cgacgagcgccgtgatcacatgtgtctggtaga ggtcgtgaaagcggttgatctggacacgtatca gGGATCCGGCCACCACCATCATCACCACtaata aGCATGCTAATCAGCCGTGGAATTCGGTCTCaG GAGgAACGATTGGTAAACCCGGTGaacgcatga gAAAGCCCCCGGAAGATCACCTTCCGGGGGCTT TtttattgcgcGGACCAAAACGAAAAAAGACGC TCGAAAGCGTCTCTTaaaactcatcgagcatca aatgaaactgcaatttattcatatcaggattat caataccatatttttgaaaaagccgtttctgta atgaaggagaaaactcaccgaggcagttccata ggatggcaagatcctggtatcggtctgcgattc cgactcgtccaacatcaatacaacctattaatt tcccctcgtcaaaaataaggttatcaagtgaga aatcaccatgagtgacgactgaatccggtgaga atggcaaaagcttatgcatttctttccagactt gttcaacaggccagccattacgctcgtcatcaa aatcactcgcatcaaccaaaccgttattcattc gtgattgcgcctgagcgagacgaaatacgcgat cgctgttaaaaggacaattacaaacaggaatcg aatgcaaccggcgcaggaacactgccagcgcat caacaatattttcacctgaatcaggatattctt ctaatacctggaatgctgttttcccggggatcg cagtggtgagtaaccatgcatcatcaggagtac ggataaaatgcttgatggtcggaagaggcataa attccgtcagccagtttagtctgaccatctcat ctgtaacatcattggcaacgctacctttgccat gtttcagaaacaactctggcgcatcgggcttcc catacaatcgatagattgtcgcacctgattgcc cgacattatcgcgagcccatttatacccatata aatcagcatccatgttggaatttaatcgcggcc tcgagcaagacgtttcccgttgaatatggctca taacaccccttgtattactgtttatgtaagcag acagttttattgttcatgatgatatatttttat cttgtgcaatgtaacatcagagattttgagaca caacgtggctttgttgaataaatcgaacttttg ctgagttgaaggatcagatcacgcatcttcccg acaacgcagaccgttccgtggcaaagcaaaagt tcaaaatcaccaactggtccacctacaacaaag ctctcatcaaccgtggctccctcactttctggc tggatgatggggcgattcaggcctggtatgagt cagcaacaccttcttcacgaggcagacctcagc gctagcggagtgtatactggcttactatgttgg cactgatgagggtgtcagtgaagtgcttcatgt ggcaggagaaaaaaggctgcaccggtgcgtcag cagaatatgtgatacaggatatattccgcttcc tcgctcactgactcgctacgctcggtcgttcga ctgcggcgagcggaaatggcttacgaacggggc ggagatttcctggaagatgccaggaagatactt aacttgggaagtgagagggccgcggcaaagccg tttttccataggctccgcccccctgacaagcat cacgaaatctgacgctcaaatcagtggtggcga aacccgacaggactataaagataccaggcgttt cccctggcggctccctcgtgcgctctcctgttc ctgcctttcggtttaccggtgtcattccgctgt tatggccgcgtttgtctcattccacgcctgaca ctcagttccgggtaggcagttcgctccaagctg gactgtatgcacgaaccccccgttcagtccgac cgctgcgccttatccggtaactatcgtcttgag tccaacccggaaagacatgcaaaagcaccactg gcagcagccactggtaattgatttagaggagtt agtcttgaagtcatgcgccggttaaggctaaac tgaaaggacaagttttggtgactgcgctcctcc aagccagttacctcggttcaaagagttggtagc tcagagaaccttcgaaaaaccgccctgcaaggc ggttttttcgttttcagagcaagagattacgcg cagaccaaaacgatctcaagaagatcatcttat taaggggtctgacgctcagtggaacggtgcacc ctgcagggctagctgataaagcgttcgcgctgc attcggcagtttaagacccactttcacatttaa gttgtttttctaatccgcatatgatcaattcaa ggccgaataagaaggctggctctgcaccttggt gatcaaataattcgatagcttgtcgtaataatg gcggcatactatcagtagtaggtgtttcccttt cttctttagcgacttgatgctcttgatcttcca atacgcaacctaaagtaaaatgccccacagcgc tgagtgcatataatgcattctctagtgaaaaac cttgt (SEQ ID NO: 1486) p15A-Kan- AACGAAAAAAGACGCTCGAAAGCGTCTCTTTTC ptet- TGGAATTTGGTACCGAGGcgtaatgctctgcca NGIgAsig- gtgttacaaccaattaaccaattctgattagaa FLAG-GFP- aaactcatcgagcatcaaatgaaactgcaattt HIS- attcatatcaggattatcaataccatatttttg NGIgAb aaaaagccgtttctgtaatgaaggagaaaactc accgaggcagttccataggatggcaagatcctg gtatcggtctgcgattccgactcgtccaacatc aatacaacctattaatttcccctcgtcaaaaat aaggttatcaagtgagaaatcaccatgagtgac gactgaatccggtgagaatggcaaaagcttatg catttctttccagacttgttcaacaggccagcc attacgctcgtcacaaaatcactcgcatcaacc aaaccgttattcattcggatgcgcctgagcgag acgaaatacgcgtttcgctgttaaaaggacaat tttcaaacaggaatcgaatgcaaccggcgcagg aacactgccagcgcatcaacaatattttcacct gaatcaggatattcttctaatacctggaatgct gttttcccggggatcgcagtggtgagtaaccat gcatcatcaggagtacggataaaatgcttgatg gtcggaagaggcataaattccgtcagccagttt agtctgaccatctcatctgtaacatcattggca acgctacctttgccatgtttcagaaacaactct ggcgcatcgggcttcccatacaatcgatagatt gtcgcacctgattgcccgacattatcgcgagcc catttatacccatataaatcagcatccatgttg gaatttaatcgcggcctcgagcaagacgtttcc cgttgaatatggctcataacaccccttgtatta ctgtttatgtaagcagacagttttattgttcat gatgatatatttttatcttgtgcaatgtaacat cagagattttgagacacaacgtggctttgtgaa taaatcgaacttgctgagttgaaggatcagatc acgcatcttcccgacaacgcagaccgttccgtg gcaaagcaaaagttcaaaatcaccaactggtcc acctacaacaaagctctcatcaaccgtggctcc ctcactttctggctggatgatggggcgattcag gcctggtatgagtcagcaacaccttcttcacga ggcagacctcagcgctagcggagtgtatactgg cttactatgttggcactgatgagggtgtcagtg aagtgcttcatgtggcaggagaaaaaaggctgc accggtgcgtcagcagaatatgtgatacaggat atattccgcttcctcgctcactgactcgctacg ctcggtcgttcgactgcggcgagcggaaatggc ttacgaacggggcggagatttcctggaagatgc caggaagatacttttacagggaagtgagagggc cgcggcaaagccgtttttccataggctccgccc ccctgacaagcatcacgaaatctgacgctcaaa tcagtggtggcgaaacccgacaggactataaag ataccaggcgtttcccctggcggctccctcgtg cgctctcctgttcctgcctttcggtttaccggt gtcattccgctgttatggccgcgtttgtctcat tccacgcctgacactcagttccgggtaggcagt tcgctccaagctggactgtatgcacgaaccccc cgttcagtccgaccgctgcgccttatccggtaa ctatcgtcttgagtccaacccggaaagacatgc aaaagcaccactggcagcagccactggtaattg atttagaggagttagtcttgaagtcatgcgccg gttaaggctaaactgaaaggacaagttttggtg actgcgctcctccaagccagttacctcggttca aagagttggtagctcagagaaccttcgaaaaac cgccctgcaaggcggttttttcgttttcagagc aagagattacgcgcagaccaaaacgatctcaag aagatcatcttattaaggggtctgacgctcagt ggaacggtgcaccctgcagggctagctgataaa gcgttcgcgctgcattcggcagtttaagaccca ctttcacatttaagttgtttttctaatccgcat atgatcaattcaaggccgaataagaaggctggc tctgcaccttggtgatcaaataattcgatagct tgtcgtaataatggcggcatactatcagtagta ggtgtttccctttcttctttagcgacttgatgc tcttgatcttccaatacgcaacctaaagtaaaa tgccccacagcgctgagtgcatataatgcattc tctagtgaaaaaccttgttggcataaaaaggct aattgattttcgagagtttcatactgttttctg taggccgtgtacctaaatgtacttttgctccat cgcgatgacttagtaaagcacatctttaaactt ttagcgttattacgtaaaaaatcttgccagctt tccccttctaaagggcaaaagtgagtatggtgc ctatctaacatctcaatggctaaggcgtcgagc aaagcccgcttattttttacatgccaatacaat gtaggctgctctacacctagcttctgggcgagt ttacgggttgttaaaccttcgattccgacctca ttaagcagctctaatgcgctgttaatcacttta cttttatctaatctagacatcattaattcctaa tttttgttgacactctatcattgatagagttat tttaccactccctatcagtgatagagaaaagtg aaaggaggtaaattATGACTAGTAAGGCAAAAC GCTTCAAGATTAACGCTATCAGTTTATCCATCT TTTTAGCGTATGCGTTGACTCCGTACTCAGAGG CAGTcGACTATAAGGATGACGACGACAAGcaat tgacggcattgacggaaggtgcaaaactgtttg agaaagagatcccgtatatcaccgaactggaag gcgacgtcgaaggtattgaaattatcataaagg cgagggtaccggtgacgcgaccacgggtaccat taaagcgaaatacatctgcactacgggcgacct gccggtcccgtgggcaaccctggtgagcaccct gagctacggtgttcagtgtttcgccaagtaccc gagccacatcaaggatttctttaagagcgccat gccggaaggttatacccaagagcgtaccatcag cttcgaaggcgacggcgtgtacaagacgcgtgc tatggttacctacgaacgcggttctatctacaa tcgtgtcacgctgactggtgagaactttaagaa agacggtcacattctgcgtaagaacgttgcatt ccaatgcccgccaagcattctgtatattttgcc tgacaccgttaacaatggcatccgcgttgagtt caaccaggcgtacgatattgaaggtgtgaccga aaaactggttaccaaatgcagccaaatgaatcg tccgttggcgggctccgcggcagtgcatatccc gcgttatcatcacattacctaccacaccaaact gagcaaagaccgcgacgagcgccgtgatcacat gtgtctggtagaggtcgtgaaagcggttgatct ggacacgtatcagGGATCCGGCCACCACCATCA TCACCACCCGCGTGCTGCACAACCGGGTACACA AGCTGCAGCCCAGGCCGACGCAGTATCCACGAA CACAAATTCAGCGTTGAGTGATGCTATGGCTTC AACTCAATCAATTCTTTTGGACACCGGCGCATA TTTAACTCGCCATATCGCCCAAAAGTCTCGTGC GGATGCAGAAAAAAATAGCGTGTGGATGTCGAA TACTGGGTATGGGCGCGACTACGCCTCTGCGCA GTACCGCCGTTTCAGCAGCAAACGCACCCAGAC TCAAATCGGGATCGATCGTAGTCTTAGTGAGAA TATGCAGATTGGCGGAGTTCTGACTTATTCCGA

CTTTTCAACATACGTTCGACCAGGCAGGGGGCA AGAATACGTTTGTACAGGCCAATCTTTACGGAA AGTACTACTTGAATGATGCCTGGTATGTCGCTG GGGACATTGGCGCAGGGAGCTTGCGTTCCCGCC TTCAAACGCAACAAAAGGCGAATTTCAATCGCA CCAGCATTCAGACTGGCCTTACACTTGGGAATA CACTTAAGATTAATCAATTTGAGATTGTGCCCA GTGCTGGgATTCGTTATAGTCGTTTATCCAGCG CAGACTATAAGTTAGGCGACGACTCTGTGAAAG TTAGCTCAATGGCCGTGAAGACGTTGACGGCTG GTTTGGATTTCGCCTATCGCTTTAAAGTTGGAA ATCTGACCGTGAAGCCGCTGCTTTCGGCCGCTT ATTTTGCAAACTACGGCAAGGGCGGCGTTAATG TCGGTGGTAAGAGTTTCGCCTATAAAGCTGACA ATCAGCAGCAATATTCGGCCGGCGTCGCGTTGT TGTATCGCAACGTGACTTTAAATGTAAACGGCT CCATCACAAAGGGCAAGCAGTTGGAGAAGCAAA AGTCAGGCCAAATCAAGATTCAAATCCGTTTCt aataaGCATGCTAATCAGCCGTGGAATTCGGTC TCaGGAGgAACGATTGGTAAACCCGGTGaacgc atgagAAAGCCCCCGGAAGATCACCTTCCGGGG GCTTTtttcattgcgcGGACCAA (SEQ ID NO: 1487)

TABLE-US-00011 TABLE 11 DNA Sequences Construct Promoter Anchor-5' Displayed protein (DNA) p15A- Gttgacactctat TGCAGTAGCAATAAAAATGCTTCG Tcggcattgacggaaggtgcaaaactg Kan-ptet- cattgatagagtta AATGACGGATCGGAAGGAATGTTA tttgagaaagagatcccgtatatcacc pelB- ttttaccactccct GGTGCTGGTACTGGCATGGACGCC gaactggaaggcgacgtcgaaggtatg FLAG- atcagtgatagag AACGGTGGCAACGGAAATATGTCT aaatttatcattaaaggcgagggtacc dasherGF aa (SEQ ID AGCGAAGAACAAGCTCGTTTACAA ggtgacgcgaccacgggtaccattaa P-HIS- NO: 1488) ATGCAGCAATTACAGCAAAACAAC agcgaaatacatctgcactacgggcg PAL ATAGTCTACTTCGACTTAGACAAGT acctgccggtcccgtgggcaaccctg ACGACATCCGTAGCGATTTTGCACA gtgagcaccctgagctacggtgttcag AATGTTGGATGCCCATGCCAACTTC tgtttcgccaagtacccgagccacatc CTTCGTTCTAATCCAAGCTACAAAG aaggatttctttaagagcgccatgccg TCACTGTTGAGGGCCACGCGGATG gaaggttatacccaagagcgtaccatc AGAGAGGCACTCCTGAATATAACA agcttcgaaggcgacggcgtgtacaa TATCCCTGGGGGAGCGCAGAGCAA gacgcgtgctatggttacctacgaacg ACGCCGTAAAAATGTACCTGCAAG cggttctatctacaatcgtgtcacgctg GCAAGGGCGTCTCGGCCGATCAAA actggtgagaactttaagaaagacggt TCTCGATCGTGAGCTATGGCAAAG cacattctgcgtaagaacgttgcattcc AGAAACCGGCTGTATTGGGACATG aatgcccgccaagcattctgtatattct ACGAAGCTGCTTACAGCAAGAATC gcctgacaccgttaacaatggcatccgc GGCGGGCCGTCTTGGTCTAC(SEQ gttgagttcaaccaggcgtacgatattg ID NO: 1489) aaggtgtgaccgaaaaactggttacca aatgcagccaaatgaatcgtccgttgg cgggctccgcggcagtgcatatcccg cgttatcatcacattacctaccacacca aactgagcaaagaccgcgacgagcg ccgtgatcacatgtgtctggtagaggtc gtgaaagcggttgatctggacacgtat cag (SEQ ID NO: 1495) p15A- Gttgacactctat GCTTTTGACCCCAATCTGGTTGGGC Acggcattgacggaaggtgcaaaact Kan-ptet- cattgatagagtta CTACGTTACCTCCAATTCCGCCTTT gtttgagaaagagatcccgtatatcacc BAN- ttttaccactccct CACTCTGCCTACG (SEQ ID NO: gaactggaaggcgacgtcgaaggtat FLAG- atcagtgatagag 1490) gaaatttatcattaaaggcgagggtacc GFP-HIS aa (SEQ ID ggtgacgcgaccacgggtaccattaa NO: 1488) agcgaaatacatctgcactacgggcg acctgccggtcccgtgggcaaccctg gtgagcaccctgagctacggtgttcag tgtttcgccaagtacccgagccacatc aaggatttctttaagagcgccatgccg gaaggttatacccaagagcgtaccatc agcttcgaaggcgacggcgtgtacaa gacgcgtgctatggttacctacgaacg cggttctatctacaatcgtgtcacgctg actggtgagaactttaagaaagacggt cacattctgcgtaagaacgttgcattcc aatgcccgccaagcattctgtatattctg cctgacaccgttaacaatggcatccgc gttgagttcaaccaggcgtacgatattg aaggtgtgaccgaaaaactggttacca aatgcagccaaatgaatcgtccgttgg cgggctccgcggcagtgcatatcccg cgttatcatcacattacctaccacacca aactgagcaaagaccgcgacgagcg ccgtgatcacatgtgtctggtagaggtc gtgaaagcggttgatctggacacgtat cag (SEQ ID NO: 1496) p15A- Gttgacactctat ATGACTAGTTAAAGCAACAAAACT Tcggcattgacggaaggtgcaaaact Kan-ptet- cattgatagagtta TGTGTTAGGCGCGGTTATACTTGGC gtttgagaaagagatcccgtatatcacc LppOmpA- ttttaccactccct TCCACCCTGCTTGCAGGTTGCTCGT gaactggaaggcgacgtcgaaggtat FLAG- atcagtgatagag CTAACGCGAAGATCGACCAGGGTA gaaatttatcattaaaggcgagggtacc GFP-HIS aa (SEQ ID TCAATCCTTACGTCGGGTTTGAAAT ggtgacgcgaccacgggtaccattaa NO: 1488) GGGATACGATTGGTTGGGACGTAT agcgaaatacatctgcactacgggcg GCCTTATAAGGGAAGTGTTGAAAA acctgccggtcccgtgggcaaccctg CGGCGCTTATAAGGCGCAGGGAGT gtgagcaccctgagctacggtgttcag ACAGTTAACGGCCAAGCTTGGGTA tgtttcgccaagtacccgagccacatc CCCCATAACAGACGATTTAGATATT aaggatttctttaagagcgccatgccg TATACCCGTTTAGGAGGAATGGTTT gaaggttatacccaagagcgtaccatc GGAGAGCCGACACGAAGTCTAATG agcttcgaaggcgacggcgtgtacaa TATATGGTAAGAACCACGACACGG gacgcgtgctatggttacctacgaacg GAGTATCCCCCGTCTTTGCAGGGGG cggttctatctacaatcgtgtcacgctg AGTGGAATATGCTATCACACCAGA actggtgagaactttaagaaagacggt GATCGCTACCCGTTTGGAATATCAA cacattctgcgtaagaacgttgcattcc TGGACGAATAATATAGGCGACGCC aatgcccgccaagcattctgtatattctg CATACGATAGGAACGCGGCCCGAC cctgacaccgttaacaatggcatccgc AAC(SEQ ID NO: 1491) gttgagttcaaccaggcgtacgatattg aaggtgtgaccgaaaaactggttacca aatgcagccaaatgaatcgtccgttgg cgggctccgcggcagtgcatatcccg cgttatcatcacattacctaccacacca aactgagcaaagaccgcgacgagcg ccgtgatcacatgtgtctggtagaggtc gtgaaagcggttgatctggacacgtat cag (SEQ ID NO: 1495) p15A- Gttgacactctat CCGCGTGCTGCACAACCGCGTACA Tcggcattgacggaaggtgcaaaact Kan-ptet- cattgatagagtta CAAGCTGCAGCCCAGGCCGACGCA gtttgagaaagagatcccgtatatcacc NGIgAsig- ttttaccactccct GTATCCACGAACACAAATTCAGCG gaactggaaggcgacgtcgaaggtat FLAG- atcagtgatagag TTGAGTGATGCTATGGCTTCAACTC gaaatttatcattaaaggcgagggtacc GFP-HIS- aa (SEQ ID AATCAATTCTTTTGGACACCGGCGC ggtgacgcgaccacgggtaccattaa NGIgAb NO: 1488) ATATTTAACTCGCCATATCGCCCAA agcgaaatacatctgcactacgggcg AAGTCTCGTGCGGATGCAGAAAAA acctgccggtcccgtgggcaaccctg AATAGCGTGTGGATGTCGAATACT gtgagcaccctgagctacggtgttcag GGGTATGGGCGCGACTACGCCTCT tgtttcgccaagtacccgagccacatc GCGCAGTACCGCCGTTTCAGCAGC aaggatttctttaagagcgccatgccg AAACGCACCCAGACTCAAATCGGG gaaggttatacccaagagcgtaccatc ATCGATCGTAGTCTTAGTGAGAATA agcttcgaaggcgacggcgtgtacaa TGCAGATTGGCGGAGTTCTGACTTA gacgcgtgctatggttacctacgaacg TTCCGACTCTCAACATACGTTCGAC cggttctatctacaatcgtgtcacgctg CAGGCAGGGGGCAAGAATACGTTT actggtgagaactttaagaaagacggt GTACAGGCCAATCTTTACGGAAAG cacattctgcgtaagaacgttgcattcc TACTACTTGAATGATGCCTGGTATG aatgcccgccaagcattctgtatattctg TCGCTGGGGACATTGGCGCAGGGA cctgacaccgttaacaatggcatccgc GCTTGCGTTCCCGCCTTCAAACGCA gttgagttcaaccaggcgtacgatattg ACAAAAGGCGAATTTCAATCGCAC aaggtgtgaccgaaaaactggttacca CAGCATTCAGACTGGCCTTACACTT aatgcagccaaatgaatcgtccgttgg GGGAATACACTTAAGATTAATCAA cgggctccgcggcagtgcatatcccg TTTGAGATTGTGCCCAGTGCTGGgA cgttatcatcacattacctaccacacca TTCGTTATAGTCGTTTATCCAGCGC aactgagcaaagaccgcgacgagcg AGACTATAAGTTAGGCGACGACTC ccgtgatcacatgtgtctggtagaggtc TGTGAAAGTTAGCTCAATGGCCGT gtgaaagcggttgatctggacacgtat GAAGACGTTGACGGCTGGTTTGGA cag (SEQ ID NO: 1495) TTTCGCCTATCGCTTTAAAGTTGGA AATCTGACCGTGAAGCCGCTGCTTT CGGCCGCTTATTTTGCAAACTACGG CAAGGGCGGCGTTAATGTCGGTGG TAAGAGTTTCGCCTATAAAGCTGAC AATCAGCAGCAATATTCGGCCGGC GTCGCGTTGTTGTATCGCAACGTGA CTTTAAATGTAAACGGCTCCATCAC AAAGGGCAAGCAGTTGGAGAAGCA AAAGTCAGGCCAAATCAAGATTCA AATCCGTTTC (SEQ ID NO: 1449) p15A- Gttgacactctat ATGACAATGACTCGTTTGAAAATTT Tcggcattgacggaaggtgcaaaact Kan-ptet- cattgatagagtta CCAAAACCCTGCTGGCCGTAATGCT gtttgagaaagagatcccgtatatcacc FLAG- ttttaccactccct TACGTCCGCAGTCGCCACTGGTTCC gaactggaaggcgacgtcgaaggtat GFP-HIS- atcagtgatagag GCATACGCAGAGAATAATGCGCAG gaaatttatcattaaaggcgagggtacc OsmY aa (SEQ ID ACAACTAACGAGTCAGCAGGGCAA ggtgacgcgaccacgggtaccattaa NO: 1488) AAAGTAGACTCCAGTATGAATAAG agcgaaatacatctgcactacgggcg GTGGGCAATTTTATGGACGACTCA acctgccggtcccgtgggcaaccctg GCTATCACCGCTAAGGTGAAAGCG gtgagcaccctgagctacggtgttcag GCGCTGGTGGACCACGACAACATC tgtttcgccaagtacccgagccacatc AAGTCCACGGACATCTCAGTTAAA aaggatttctttaagagcgccatgccg ACGGACCAAAAGGTAGTAACCTTA gaaggttatacccaagagcgtaccatc AGCGGGTTCGTAGAAAGCCAGGCG agcttcgaaggcgacggcgtgtacaa CAAGCAGAGGAAGCGGTAAAAGTC gacgcgtgctatggttacctacgaacg GCTAAAGGCGTAGAAGGGGTCACT cggttctatctacaatcgtgtcacgctg TCGGTgTCAGACAAGTTGCATGTGC actggtgagaactttaagaaagacggt GTGACGCAAAGGAAGGATCAGTAA cacattctgcgtaagaacgttgcattcc AGGGTTATGCCGGAGATACGGCAA aatgcccgccaagcattctgtatattctg CGACCTCTGAGATCAAAGCGAAAT cctgacaccgttaacaatggcatccgc TACTGGCAGACGACATTGTTCCCTC gttgagttcaaccaggcgtacgatattg GCGTCATGTTAAAGTCGAAACGAC aaggtgtgaccgaaaaactggttacca TGATGGCGTAGTCCAGCTTTCGGGT aatgcagccaaatgaatcgtccgttgg ACAGTTGACTCCCAAGCACAAAGT cgggctccgcggcagtgcatatcccg GATCGCGCGGAATCTATTGCAAAG cgttatcatcacattacctaccacacca GCGGTGGACGGAGTGAAATCCGTC aactgagcaaagaccgcgacgagcg AAAAACGATCTTAAAACGAAA ccgtgatcacatgtgtctggtagaggtc (SEQ ID NO: 1492) gtgaaagcggttgatctggacacgtat cag (SEQ ID NO: 1495) p15A- Gttgacactctat ATGGTTTTCCAACCCATCAGCGAAT Tcggcattgacggaaggtgcaaaact invasinN- cattgatagagtta TTTTGCTGATTCGTAACGCTGGGAT gtttgagaaagagatcccgtatatcacc FLAG- ttttaccactccct GTCCATGTATTTTAACAAGATCATT gaactggaaggcgacgtcgaaggtat GFP-HIS atcagtgatagag TCTTTTAACATCATTTCACGTATCG gaaatttatcattaaaggcgagggtacc aa (SEQ ID TTATTTGCATTTTTCTTATCTGTGGT ggtgacgcgaccacgggtaccattaa NO: 1488) ATGTTCATGGCCGGTGCATCTGAAA agcgaaatacatctgcactacgggcg AGTATGATGCAAACGCACCCCAAC acctgccggtcccgtgggcaaccctg AGGTGCAGCCATACTCGGTTTCATC gtgagcaccctgagctacggtgttcag ATCAGCGTTCGAGAATCTGCACCCC tgtttcgccaagtacccgagccacatc AATAACGAGATGGAGTCGAGTATC aaggatttctttaagagcgccatgccg AACCCTTTTAGTGCTTCGGACACCG gaaggttatacccaagagcgtaccatc AGCGTAATGCAGCTATCATCGATC agcttcgaaggcgacggcgtgtacaa GTGCTAACAAGGAACAAGAAACGG gacgcgtgctatggttacctacgaacg AAGCAGTCAACAAAATGATCTCCA cggttctatctacaatcgtgtcacgctg CTGGCGCTCGTTTAGCTGCCAGCGG actggtgagaactttaagaaagacggt TCGCGCGTCCGATGTGGCGCACAG cacattctgcgtaagaacgttgcattcc TATGGTAGGGGATGCGGTCAACCA aatgcccgccaagcattctgtatattctg GGAGATTAAACAATGGCTGAATCG cctgacaccgttaacaatggcatccgc CTTCGGCACTGCTCAAGTGAATTTA gttgagttcaaccaggcgtacgatattg AATTTTGACAAGAACTTCTCGTTAA aaggtgtgaccgaaaaactggttacca AGGAGTCTTCGCTTGACTGGTTGGC aatgcagccaaatgaatcgtccgttgg CCCATGGTACGATTCGGCGTCATTC cgggctccgcggcagtgcatatcccg CTTTTCTTTTCTCAGTTGGGCATCC cgttatcatcacattacctaccacacca GTAACAAGGACAGTCGTAATACAC aactgagcaaagaccgcgacgagcg TTAACCTTGGTGTTGGCATTCGCAC ccgtgatcacatgtgtctggtagaggtc ATTAGAAAATGGTTGGTTGTATGGC gtgaaagcggttgatctggacacgtat CTGAACACCTTTTACGACAATGACT cag (SEQ ID NO: 1495) TAACGGGACACAATCACCGTATCG GGCTGGGCGCCGAGGCGTGGACTG ACTACTTGCAGTTAGCCGCGAATG GGTACTTCCGTCTTA ATGGTTGGCACTCTTCCCGTGACTT CAGCGACTACAAAGAACGCCCTGC TACCGGGGGAGATTTGCGTGCGAA TGCGTACCTGCCCGCTCTTCCGCAA CTTGGCGGGAAGTTAATGTATGAG CAGTATACTGGGGAACGCGTGGCT CTGTTCGGAAAGGACAACCTGCAG CGCAACCCATACGCTGTCACTGCG GGTATCAACTATACGCCAGTTCCGT TGCTGACGGTCGGCGTGGATCAAC GTATGGGGAAGTCGAGTAAACATG AAACGCAATGGAATTTACAAATGA ACTATCGCTTAGGGGAGAGTTTCCA AAGTCAGCTTAGCCCTTCGGCGGTC GCAGGGACTCGTTTGCTTGCTGAGT CCCGCTACAACCTGGTTGATCGCAA TAACAATATCGTACTGGAATACCA GAAACAACAAGTGGTTAAGCTGAC GTTGAGCCCTGCGACCATCAGTGG ATTGCCCGGACAAGTTTACCAGGT AAATGCCCAGGTCCAGGGGGCCTC TGCGGTTCGCGAAATTGTCTGGTCA GACGCAGAATTAATCGCTGCAGGA GGCACCTTAACGCCACTTTCCACTA CACAATTCAATTTAGTCCTTCCCCC ATACAAACGTACCGCCCAGGTATC GCGCGTAACTGATGACTTAACTGCT AATTTTTATTCACTGTCGGCGTTAG CAGTTGACCATCAAGGCAACCGTA GTAATTCCTTCACATTATCTGTAAC GGTGCAGCAGCCGCAACTGACGCT TACCGCAGCGGTCATTGGTGATGG GGCCCCAGCTAATGGGAAAACCGC AATCACTGTCGAgTTCACAGTTGCA GATTTTGAAGGCAAGCCGCTGGCG GGTCAGGAGGTTGTGATTACGACT AATAACGGTGCTCTTCCTAATAAGA TTACTGAAAAGACTGACGCTAACG GCGTTGCCCGCATTGCCCTTACGAA CACAACCGATGGGGTCACGGTAGT TACCGCAGAGGTCGAGGGGCAACG CCAATCCGTTGACACGCACTTCGTT AAGGGTACTATCGCGGCCGATAAA AGCACGCTGGCCGCGGT(SEQ ID NO: 1493) p15A- Gttgacactctat ATGTTAATCAATAGAAACATTGTCG Tcggc attgacggaaggtgcaaaact yiaT- cattgatagagtta CCCTTTTTGCCCTGCCATTCATGGC gtttgagaaagagatcccgtatatcac FLAG- ttttaccactccct GAGTGCGACCGCTTCCGAGTTAAG cgaactggaaggcgacgtcgaaggtat GFP-HIS atcagtgatagag CATAGGGGCCGGCGCTGCGTATAA gaaatttatcattaaaggcgagggtac

aa (SEQ ID TGAGAGTCCTTACCGTGGCTATAAT cggtgacgcgaccacgggtaccattaa NO: 1488) GAAAACACAAAGGCAATCCCCCTT agcgaaatacatctgcactacgggcg ATCTCGTATGAAGGCGACACCTTCT acctgccggtcccgtgggcaaccctg ATGTACGTCAGACTACATTAGGTTT gtgagcaccctgagctacggtgttcag CATCTTAAGCCAGTCCGAGAAAAA tgtttcgccaagtacccgagccacatc CGAGTTATCGCTGACAGCTTCATGG aaggatttctttaagagcgccatgccg ATGCCATTGGAATTCGACCCGACA gaaggttatacccaagagcgtaccatc GATAATGATGATTATGCGATGCAG agcttcgaaggcgacggcgtgtacaa CAGCTGGACAAACGGGATTCGACA gacgcgtgctatggttacctacgaacg GCTATGGCCGGCGTGGCTTGGTATC cggttctatctacaatcgtgtcacgctg ACCACGAGCGGTGGGGAACTGTCA actggtgagaactttaagaaagacggt AAGCTTCCGCCGCCGCTGACGTGTT cacattctgcgtaagaacgttgcattcc AGACAACAGCAATGGCTGGGTGGG aatgcccgccaagcattctgtatattct GGAATTAAGCGTGTTCCATAAGAT gcctgacaccgttaacaatggcatccgc GCAGATAGGTAGATTATCCCTTACA gttgagttcaaccaggcgtacgatattg CCGGCTTTGGGAGTCCTGTATTATG aaggtgtgaccgaaaaactggttacca ATGAGAACTTTTCCGACTATTATTA aatgcagccaaatgaatcgtccgttgg TGGGATTTCTGAGTCTGAAAGTCGT cgggctccgcggcagtgcatatcccgc CGGAGCGGTCTTGCGTCGTACTCGG gttatcatcacattacctaccacacca CGCAAGACGCGTGGGTGCCTTATG aactgagcaaagaccgcgacgagcgc TATCTTTGACAGCGAAGTATCCAAT cgtgatcacatgtgtctggtagaggtc AGGCGAGCACGTGGTATTGATGGC gtgaaagcggttgatctggacacgtat AAGTGCTGGTTATTCCGAGTTGCCC cag (SEQ ID NO: 1495) GAAGAAATTACTGACAGTCCTATG ATAGACCGT (SEQ ID NO: 1450) p15A- Gttgacactctat ATGATTACGCATGGCTGTTATACCC Acggcattgacggaaggtgcaaaact intiminN- cattgatagagtta GTACGCGTCATAAACACAAGTTGA gtttgagaaagagatcccgtatatcac FLAG- ttttaccactccct AGAAAACTCTGATCATGTTATCCGC cgaactggaaggcgacgtcgaaggtat GFP-HIS atcagtgatagag TGGACTTGGACTTTmTTTACGTG gaaatttatcattaaaggcgagggtac aa (SEQ ID AATCAGAACTCTTTCGCTAATGGGG cggtgacgcgaccacgggtaccattaa NO: 1488) AAAATTATTTTAAACTGGGATCAG agcgaaatacatctgcactacgggcg ACAGCAAATTACTTACGCATGACTC acctgccggtcccgtgggcaaccctg ATACCAGAATCGTCTGTTTTATACG gtgagcaccctgagctacggtgttcag CTGAAAACTGGTGAaACCGTTGCAG tgtttcgccaagtacccgagccacatc ATTTAAGTAAAAGTCAGGACATTA aaggatttctttaagagcgccatgccg ACCTGTCAACTATTTGGTCACTTAA gaaggttatacccaagagcgtaccatc TAAACACTTATATTCGAGCGAATCG agcttcgaaggcgacggcgtgtacaa GAAATGATGAAAGCTGCACCGGGG gacgcgtgctatggttacctacgaacg CAACAAATCATCTTGCCCCTGAAG cggttctatctacaatcgtgtcacgctg AAATTGCCCTTTGAATACTCCGCTT actggtgagaactttaagaaagacggt TGCCCTTGCTGGGCTCGGCTCCTCT cacattctgcgtaagaacgttgcattcc GGTAGCCGCCGGAGGCGTTGCCGG aatgcccgccaagcattctgtatattct TCACACTAATAAGCTGACAAAAAT gcctgacaccgttaacaatggcatccgc GTCACCCGACGTGACGAAGAGCAA gttgagttcaaccaggcgtacgatattg CATGACGGATGATAAGGCTTTAAA aaggtgtgaccgaaaaactggttacca TTACGCAGCTCAGCAAGCGGCCTC aatgcagccaaatgaatcgtccgttgg GTTGGGAAGTCAGTTACAGAGTCG cgggctccgcggcagtgcatatcccg TTCGTTAAATGGTGATTATGCTAAG cgttatcatcacattacctaccacacca GATACCGCATTGGGTATTGCCGGC aactgagcaaagaccgcgacgagcg AACCAAGCGTCGAGCCAACTTCAG ccgtgatcacatgtgtctggtagaggtc GCATGGTTGCAACATTACGGCACT gtgaaagcggttgatctggacacgtat GCTGAAGTAAATCTGCAATCAGGT cag (SEQ ID NO: 1496) AATAATTTTGACGGTAGTTCCCTGG ATTTCCTTTTACCTTTTTACGATTCA GAAAAGATGTTGGCTTTCGGACAG GTGGGGGCGCGTTACATCGATTCA CGTTTTACCGCTAACTTGGGGGCCG GTCAACGCTTCTTCTTACCTGCCAA TATGTTGGGCTATAATGTATTTATC GACCAGGACTTCAGTGGTGACAAT ACACGTCTGGGAATTGGTGGAGAG TAtTGGCGCGATTACTTTAAGTCAT CTGTAAATGGCTATTTTCGCATGAG CGGTTGGCATGAAAGTTACAACAA GAAAGACTACGATGAGCGCCCCGC GAACGGGTTTGACATCCGTTTTAAT GGTTATTTGCCATCTTATCCCGCCT TGGGAGCTAAATTAATCTACGAGC AATACTATGGAGATAACGTAGCTTT GTTTAATAGCGACAAGTTACAGTCT AATCCAGGAGCGGCTACAGTGGGA GTTAATTATACCCCAATCCCACTGG TCACAATGGGAATCGATTATCGCC ACGGGACTGGTAATGAAAACGATT TATTATACTCCATGCAGTTTCGTTA TCAGTTCGATAAGAGTTGGTCGCA GCAGATTGAGCCTCAATATGTTAAC GAATTACGTACCTTGTCCGGCAGTC GCTACGATCTGGTACAACGCAATA ACAATATCATCCTTGAGTATAAGA AACAGGACATTCTGTCTTTGAACAT TCCACATGATATTAATGGTACCGAG CACTCAACACAAAAAATTCAGCTG ATTGTGAAATCAAAGTATGGACTG GACCGTATCGTGTGGGATGATAGC GCTCTGCGCAGTCAGGGTGGACAG ATCCAGCACTCGGGTAGCCAGTCT GCCCAAGACTACCAGGCTATCCTG CCAGCGTATGTCCAAGGGGGAAGT AACATCTACAAAGTTACAGCTCGC GCCTATGACCGCAACGGTAATTCTA GTAATAATGTGCAGTTGACAATTAC GGTGCTGTCCAATGGGCAGGTCGT CGATCAGGTAGGTGTGACGGATTTT ACAGCCGATAAAACCTCTGCGAAG GCACiATAACGCGGATACCATCACA TACACTGCCACTGTAAAAAAAAAC GGTGTCGCGCAGGCAAACGTTCCT GTTAGCTTCAACATCGTGTCGGGTA CAGCCACCCTTGGGGCCAACTCGG CAAAGACTGACGCGAATGGCAAGG CTACAGTCACGTTGAAATCCTCGAC ACCAGGACAGGTCGTTGTGTCTGCC AAGACAGCAGAGATGACCTCCGCC CTTAATGCATCTGCTGTTATCTTCTT CGATCAAACGAAGGCATCT (SEQ ID NO: 1494)

TABLE-US-00012 TABLE 12 Amino Acid Sequences Construct Anchor Displayed Protein (aa) p15A-Kan- CSSNKNASNDGSEGMLGAGT TALTEGAKLFEKEIPYITELEGDVEGMKFIIKG ptet-pelB- GMDANGGNGNMSSEEQARL EGTGDATTGTIKAKYICTTGDLPVPWATLVST FLAG- QMQQLQQNNIVYFDLDKYDI LSYGVQCFAKYPSHIKDFFKSAMPEGYTQERT dasherGFP- RSDFAQMLDAHANFLRSNPSY ISFEGDGVYKTRAMVTYERGSIYNRVTLTGEN HIS-PAL KVTVEGHADERGTPEYNISLG FKKDGHILRKNVAFQCPPSILYILPDTVNNGI ERRANAVKMYLQGKGVSAD RVEFNQAYDIEGVTEKLVTKCSQMNRPLAGSA QISIVSYGKEKPAVLGHDEAA AVHIPRYHHITYHTKLSKDRDERRDHMCLVE YSKNRRAVLVY VVKAVDLDTYQ (SEQ ID NO: 1497) (SEQ ID NO: 1502) p15A-Kan- MTSAFDPNLVGPTLPPIPPFTL TALTEGAKLFEKEIPYITELEGDVEGMKFIIKG ptet-BAN- PT (SEQ ID NO: 1498) EGTGDATTGTIKAKYICTTGDLPVPWATLVST FLAG- LSYGVQCFAKYPSHIKDFFKSAMPEGYTQERT GFP-HIS ISFEGDGVYKTRAMVTYERGSIYNRVTLTGEN FKKDGHILRKNVAFQCPPSILYILPDTVNNGI RVEFNQAYDIEGVTEKLVTKCSQMNRPLAGSA AVHIPRYHHITYHTKLSKDRDERRDHMCLVE VVKAVDLDTYQ (SEQ ID NO: 1502) p15A-Kan- MTSKATKLVLGAVILGSTLLA TALTEGAKLFEKEIPYITELEGDVEGMKFIIKG ptet- GCSSNAKIDQGINPYVGFEMG EGTGDATTGTIKAKYICTTGDLPVPWATLVST LppOmpA- YDWLGRMPYKGSVENGAYK LSYGVQCFAKYPSHIKDFFKSAMPEGYTQERT FLAG- AQGVQLTAKLGYPITDDLDIY ISFEGDGVYKTRAMVTYERGSIYNRVTLTGEN GFP-HIS TRLGGMVWRADTKSNVYGK FKKDGHILRKNVAFQCPPSILYILPDTVNNGI NHDTGVSPVFAGGVEYAITPEI RVEFNQAYDIEGVTEKLVTKCSQMNRPLAGSA ATRLEYQWTNNIGDAHTIGTR AVHIPRYHHITYHTKLSKDRDERRDHMCLVE PDN (SEQ ID NO: 1499) VVKAVDLDTYQ (SEQ ID NO: 1502) p15A-Kan- PRAAQPRTQAAAQADAVSTN TALTEGAKLFEKEIPYITELEGDVEGMKFIIKG ptet- TNSALSDAMASTQSILLDTGA EGTGDATTGTIKAKYICTTGDLPVPWATLVST NGIgAsig- YLTRHIAQKSRADAEKNSVW LSYGVQCFAKYPSHIKDFFKSAMPEGYTQERT FLAG- MSNTGYGRDYASAQYRRFSS ISFEGDGVYKTRAMVTYERGSIYNRVTLTGEN GFP-HIS- KRTQTQIGIDRSLSENMQIGG FKKDGHILRKNVAFQCPPSILYILPDTVNNGI NGIgAb VLTYSDSQHTFDQAGGKNTFV RVEFNQAYDIEGVTEKLVTKCSQMNRPLAGSA QANLYGKYYLNDAWYVAGD AVHIPRYHHITYHTKLSKDRDERRDHMCLVE IGAGSLRSRLQTQQKANFNRT VVKAVDLDTYQ SIQTGLTLGNTLKINQFEIVP (SEQ ID NO: 1502) SAGIRYSRLSSADYKLGDDSV KVSSMAVKTLTAGLDFAYRFK VGNLTVKPLLSAAYFANYGKG GVNVGGKSFAYKADNQQQYS AGVALLYRNVTLNVNGSITKG KQLEKQKSGQIKIQIRF (SEQ ID NO: 1464) p15A-Kan- MTMTRLKISKTLLAVMLTSAV TALTEGAKLFEKEIPYITELEGDVEGMKFIIKG ptct-FLAG- ATGSAYAENNAQTTNESAGQ EGTGDATTGTIKAKYICTTGDLPVPWATLVST GFP-HIS- KVDSSMNKVGNFMDDSAITA LSYGVQCFAKYPSHIKDFFKSAMPEGYTQERT OsmY KVKAALVDHDNIKSTDISVKT ISFEGDGVYKTRAMVTYERGSIYNRVTLTGEN DQKVVTLSGFVESQAQAEEA FKKDGHILRKNVAFQCPPSILYILPDTVNNGI VKVAKGVEGVTSVSDKLHVR RVEFNQAYDIEGVTEKLVTKCSQMNRPLAGSA DAKEGSVKGYAGDTATTSEIK AVHIPRYHHITYHTKLSKDRDERRDHMCLVE AKLLADDIVPSRHVKVETTDG VVKAVDLDTYQTALTEGAKLFEKEIPYITELE VVQLSGTVDSQAQSDRAESIA GDVEGMKFIIKGEGTGDATTGTIKAKYICTTG KAVDGVKSVKNDLKTK DLPVPWATLVSTLSYGVQCFAKYPSHIKDFFK (SEQ ID NO: 1500) SAMPEGYTQERTISFEGDGVYKTRAMVTYER GSIYNRVTLTGENFKKDGHILRKNVAFQCPPSI LYILPDTVNNGIRVEFNQAYDIEGVTEKLVTK CSQMNRPLAGSAAVHIPRYHHITYHTKLSKDR DERRDHMCLVEVVKAVDLDTYQ (SEQ ID NO: 1503) p15A- MVFQPISEFLLIRNAGMSMYF TALTEGAKLFEKEIPYITELEGDVEGMKFIIKG invasinN- NKIISFNIISRIVICIFLICGM EGTGDATTGTIKAKYICTTGDLPVPWATLVST FLAG- FMAGASEKYDANAPQQVQPYSV LSYGVQCFAKYPSHIKDFFKSAMPEGYTQERT GFP-HIS SSSAFENLHPNNEMESSINPFS ISFEGDGVYKTRAMVTYERGSIYNRVTLTGEN ASDTERNAAIIDRANKEQETE FKKDGHILRKNVAFQCPPSILYILPDTVNNGI AVNKMISTGARLAASGRASD RVEFNQAYDIEGVTEKLVTKCSQMNRPLAGSA VAHSMVGDAVNQEIKQWLNR AVHIPRYHHITYHTKLSKDRDERRDHMCLVE FGTAQVNLNFDKNFSLKESSL VVKAVDLDTYQ DWLAPWYDSASFLFFSQLGIR (SEQ ID NO: 1502) NKDSRNTLNLGVGIRTLENG WLYGLNTFYDNDLTGHNHRI GLGAEAWTDYLQLAANGYFR LNGWHSSRDFSDYKERPATG GDLRANAYLPALPQLGGKLM YEQYTGERVALFGKDNLQRN PYAVTAGINYTPVPLLTVGVD QRMGKSSKHETQWNLQMNY RLGESFQSQLSPSAVAGTRLL AESRYNLVDRNNNIVLEYQK QQVVKLTLSPATISGLPGQVY QVNAQVQGASAVREIVWSDA ELIAAGGTLTPLSTTQFNLVLP PYKRTAQVSRVTDDLTANFYS LSALAVDHQGNRSNSFTLSVT VQQPQLTLTAAVIGDGAPANG KTAITVEFTVADFEGKPLAGQ EVVnTNNGALPNKITEKTDA NGVARIALTNTTDGVTVVTAE VEGQRQSVDTHFVKGTIAAD KSTLAAV (SEQ ID NO: 990) p15A-yiaT- MLINRNIVALFALPFMASATA TALTEGAKLFEKEIPYITELEGDVEGMKFTIKG FLAG- SELSIGAGAAYNESPYRGYNE EGTGDATTGTIKAKYICTTGDLPVPWATLVST GFP-HIS NTKAIPLISYEGDTFYVRQTTL LSYGVQCFAKYPSHIKDFFKSAMPEGYTQERT GFILSQSEKNELSLTASWMPLE ISFEGDGVYKTRAMVTYERGSIYNRVTLTGEN FDPTDNDDYAMQQLDKRDST FKKDGHILRKNVAFQCPPSILYILPDTVNNGI AMAGVAWYHHERWGTVKAS RVEFNQAYDIEGVTEKLVTKCSQMNRPLAGSA AAADVLDNSNGWVGELSVFH AVHIPRYHHITYHTKLSKDRDERRDHMCLVE KMQIGRLSLTPALGVLYYDEN VVKAVDLDTYQ (SEQ ID NO: 1502) FSDYYYGISESESRRSGLASYS AQDAWVPYVSLTAKYPIGEH VVLMASAGYSELPEEITDSPMI DR (SEQ ID NO: 1465) p15A- MITHGCYTRTRHKHKLKKTLI TALTEGAKLFEKEIPYITELEGDVEGMKFIIKG intiminN- MLSAGLGLFFYVNQNSFANG EGTGDATTGTIKAKYICTTGDLPVPWATLVST FLAG- ENYFKLGSDSKLLTHDSYQNR LSYGVQCFAKYPSHIKDFFKSAMPEGYTQERT GFP-HIS LFYTLKTGETVADLSKSQDIN ISFEGDGVYKTRAMVTYERGSIYNRVTLTGEN LSTIWSLNKHLYSSESEMMKA FKKDGHILRKNVAFQCPPSILYILPDTVNNGI APGQQIILPLKKLPFEYSALP RVEFNQAYDIEGVTEKLVTKCSQMNRPLAGSA LLGSAPLVAAGGVAGHTNKLT AVHIPRYHHITYHTKLSKDRDERRDHMCLVE KMSPDVTKSNMTDDKALNYA VVKAVDLDTYQ (SEQ ID NO: 1502) AQQAASLGSQLQSRSLNGDY AKDTALGIAGNQASSQLQAW LQHYGTAEVNLQSGNNFDGS SLDFLLPFYDSEKMLAFGQVG ARYIDSRFTANLGAGQRFFLP ANMLGYNVFIDQDFSGDNTR LGIGGEYWRDYFKSSVNGYFR MSGWHESYNKKDYDERPANG FDIRFNGYLPSYPALGAKLIY EQYYGDNVALFNSDKLQSNP GAATVGVNYTPIPLVTMGIDY RHGTGNENDLLYSMQFRYQF DKSWSQQIEPQYVNELRTLSG SRYDLVQRNNNIILEYKKQDIL SLNIPHDINGTEHSTQKIQLIV KSKYGLDRIVWDDSALRSQGG QIQHSGSQSAQDYQAILPAYV QGGSNIYKVTARAYDRNGNS SNNVQLTITVLSNGQVVDQVG VTDFTADKTSAKADNADTITY TATVKKNGVAQANVPVSFNI VSGTATLGANSAKTDANGKA TVTLKSSTPGQVVVSAKTAEM TSALNASAVIFFDQTKAS (SEQ ID NO: 1501)

Example 2. Surface Display of Nanobody A4 and EGFR Using E. coli Nissle

[0513] E. coli Nissle cells expressing and displaying nanobody A4 were designed and tested using flow cytometry. Generally, nanobody A4 was fused to an anchor domain by a linker (FIG. 6). In vitro staining and analysis by flow cytometry showed that displayed nanobody A4 bound to CD47-IgG.

[0514] Nanbody A4 was shown to bind CD47 using either pelB-PAL or yiaT as an anchor domain (FIG. 7). The constructs are shown in Table 13 below.

TABLE-US-00013 TABLE 13 Strains for Nanobody A4 surface display (FIG. 7) Strain Displayed Number Construct Promoter Anchor Protein SYN1557 E. coli Nissle delta PAL: CmR SYN6816 pelB-A4- GTTGACACTC CSSNKNASN MKYLLPT Flag-PAL TATCATTGAT DGSEGMLGA AAAGLLL AGAGTTATTT GTGMDANGG LAAQPAM TACCACTCCC NGNMSSEEQ AQVQLVE TATCAGTGAT ARLQMQQLQ SGGGLVE AGAGAA QNNIVYFDL PGGSLRL (SEQ ID NO: DKYDIRSDF SCAASGI 1488) AQMLDAHAN IFKINDM FLRSNPSYK GWYRQAP VTVEGHADE GKRREWV RGTPEYNTS AASTGGD LGERRANAV EATYRDS KMYLQGKGV VKDRFTI SADQISIVS SRDAKNS YGKEKPAVL VFLQMNS GHDEAAYSK LKPEDTA NRRAVLVY VYYCTAV (SEQ ID ISTDRDG NO: TEWRRYW 1497) GQGTQVT VSSGGLP ET (SEQ ID NO: 1505) SYN6817 pelB-A4- GTTGACACTC MLINRNIVA MKYLLPT Flag- TATCATTGAT LFALPFMAS AAAGLLL YiaT AGAGTTATTT ATASELSIG LAAQPAM TACCACTCCC AGAAYNESP AQVQLVE TATCAGTGAT YRGYNENTK SGGGLVE AGAGAA AIPLISYEG PGGSLRL (SEQ ID NO: DTFYVRQTT SCAASGI 1488) LGFILSQSE IFKINDM KNELSLTAS GWYRQAP WMPLEFDPT GKRREWV DNDDYAMQQ AASTGGD LDKRDSTAM EAIYRDS AGVAWYHHE VKDRFTI RWGTVKASA SRDAKNS AADVLDNSN VFLQMNS GWVGELSVF LKPEDTA HKMQIGRLS VYYCTAV LTPALGVLY ISTDRDG YDENFSDYY TEWRRYW YGISESESR GQGTQVT RSGLASYSA VSSGGLP QDAWVPYVS ET LTAKYPIGE (SEQ ID HVVLMASAG NO: YSELPEEIT 1505) DSPMIDR (SEQ ID NO: 1465)

[0515] E. coli Nissle cells expressing and displaying aEGFR were designed and tested using flow cytometry. Integrated aEGFR-myc showed similar results as the negative control. Strains SYN7082, SYN7083, SYN7189, and SYN7192 showed EGFR expressing on the surface of the Nissle cells (FIG. 9). The constructs are shown in Table 14 below.

TABLE-US-00014 TABLE 14 Strains for aEGFR surface display (FIG. 8) Strain Displayed Number Construct Promoter Anchor Protein SYN094 negative TCATAAAAAA MITHGCYTRTRHKHKLKK MAQVQLQESGGG control TTTATTTGCTT TLIMLSAGLGLFFYVNQNS LVQAGGSLLLSCA TCAGGAAAAT FANGENYFKLGSDSKLLTH ASGRTFSSYAMG TTTTCTGTATA DSYQNRLFYTLKTGETVAD WFRQAPGKEREFV ATAGATTCAT LSKSQDINLSTIWSLNKHLY AAINWSGGSTSYA AAATTTGAGA SSESEMMKAAPGQQIILPL DSVKGRFTISRDN GAGGAGTT KKLPFEYSALPLLGSAPLV TKNTVYLQMNSL (SEQ ID NO: AAGGVAGHTNKLTKMSPD KPEDTAAFYCAAT 1506) VTKSNMTDDKALNYAAQQ YNPYSRDHYFPRMT AASLGSQLQSRSLNGDYAK TEYDYWGQGTQVTV DTALGIAGNQASSQLQAW SS LQHYGTAEVNLQSGNNFD (SEQ ID GSSLDFLLPFYDSEKMLAF NO: 1509) GQVGARYIDSRFTANLGAG QRFFLPANMLGYNVFIDQD FSGDNTRLGIGGEYWRDYF SYN7049 aEGFR- KSSVNGYFRMSGWHESYN myc KKDYDERPANGFDIRFNGY (integrated ) LPSYPALGAKLIYEQYYGD NVALFNSDKLQSNPGAATV GVNYTPIPLVTMGIDYRHG TGNENDLLYSMQFRYQFDK SWSQQIEPQYVNELRTLSG SRYDLVQRNNNIILEYKKQ DILSLNIPHDINGTEHSTQ KIQLIVKSKYGLDRIVWDD SALRSQGGQIQHSGSQSAQ DYQAILPAYVQGGSNIYKV TARAYDRNGNSSNNVQLTI TVLSNGQVVDQVGVTDFTA DKTSAKADNADTITYTATV KKNGVAQANVPVSFNIVSG TATLGANSAKTDANGKATV TLKSSTPGQVVVSAKTAEM TSALNASAVIFFDGA (SEQ ID NO: 1508) SYN7082 FLAG- GTTGACACTCT MITHGCYTRTRHKHKLKK AQVQLQESGGGL aEGFR- ATCATTGATA TLIMLSAGLGLFFYVNQNS VQAGGSLLLSCAA myc in GAGTTATTTTA FANGENYFKLGSDSKLLTH SGRTFSSYAMGWF SYN094 CCACTCCCTAT DSYQNRLFYTLKTGETVAD RQAPGKEREFVAA CAGTGATAGA LSKSQDINLSTIWSLNKHLY INWSGGSTSYADS GAA (SEQ ID SSESEMMKAAPGQQIILPL VKGRFTISRDNTK NO: 1488) KKLPFEYSALPLLGSAPLV NTVYLQMNSLKPE AAGGVAGHTNKLTKMSPD DTAAFYCAATYNP VTKSNMTDDKALNYAAQQ YSRDHYFPRMTTE AASLGSQLQSRSLNGDYAK YDYWGQGTQVTV DTALGIAGNQASSQLQAW SSEPKTPKPQP LQHYGTAEVNLQSGNNFDG (SEQ ID NO: SSLDFLLPFYDSEKMLAFG 1510) QVGARYIDSRFTANLGAGQ RFFLPANMLGYNVFIDQDF SGDNTRLGIGGEYWRDYFK SSVNGYFRMSGWHESYNKK DYDERPANGFDIRFNGYLP SYPALGAKLIYEQYYGD NVALFNSDKLQSNPGAAT VGVNYTPIPLVTMGIDYRH GTGNENDLLYSMQFRYQF DKSWSQQIEPQYVNELRTL SGSRYDLVQRNNNIILEYK KQDILSLNIPHDINGTEHST QKIQLIVKSKYGLDRIVWD DSALRSQGGQIQHSGSQSA QDYQAILPAYVQGGSNIYK VTARAYDRNGNSSNNVQL TITVLSNGQVVDQVGVTDF TADKTSAKADNADTITYTA TVKKNGVAQANVPVSFNIV SGTATLGANSAKTDANGK ATVTLKSSTPGQVVVSAKT AEMTSALNASAVIFFDQTK AS (SEQ ID NO: 1501) SYN7083 FLAG- GTTGACACTCT MITHGCYTRTRHKHKLKK AQVQLQESGGGL aEGFR- ATCATTGATA TLIMLSAGLGLFFYVNQNS VQAGGSLLLSCAA myc in GAGTTATTTTA FANGENYFKLGSDSKLLTH SGRTFSSYAMGWF SYN1557 CCACTCCCTAT DSYQNRLFYTLKTGETVAD RQAPGKEREFVAA CAGTGATAGA LSKSQDINLSTIWSLNKHLY INWSGGSTSYADS GAA (SEQ ID SSESEMMKAAPGQQIILPL VKGRFTISRDNTK NO: 1488) KKLPFEYSALPLLGSAPLV NTVYLQMNSLKPE AAGGVAGHTNKLTKMSPD DTAAFYCAATYNP VTKSNMTDDKALNYAAQQ YSRDHYFPRMTTE AASLGSQLQSRSLNGDYAK YDYWGQGTQVTV DTALGIAGNQASSQLQAW SSEPKTPKPQP LQHYGTAEVNLQSGNNFD (SEQ ID GSSLDFLLPFYDSEKMLAF NO: 1510) GQVGARYIDSRFTANLGAG QRFFLPANMLGYNVFIDQD FSGDNTRLGIGGEYWRDYF KSSVNGYFRMSGWHESYN KKDYDERPANGFDIRFNGY LPSYPALGAKLIYEQYYGD NVALFNSDKLQSNPGAAT VGVNYTPIPLVTMGIDYRH GTGNENDLLYSMQFRYQF DKSWSQQIEPQYVNELRTL SGSRYDLVQRNNNIILEYK KQDILSLNIPHDINGTEHST QKIQLIVKSKYGLDRIVWD DSALRSQGGQIQHSGSQSA QDYQAILPAYVQGGSNIYK VTARAYDRNGNSSNNVQL TITVLSNGQVVDQVGVTDF TADKTSAKADNADTITYTA TVKKNGVAQANVPVSFNIV SGTATLGANSAKTDANGK ATVTLKSSTPGQVVVSAKT AEMTSALNASAVIFFDQTK AS(SEQ ID NO: 1501) SYN7189 FLAG- GTTGACACTCT MITHGCYTRTRHKHKLKK QVKLEESGGGSVQ aEGFR1- ATCATTGATA TLIMLSAGLGLFFYVNQNS TGGSLRLTCAASG His-myc GAGTTATTTTA FANGENYFKLGSDSKLLTH RTSRSYGMGWFR CCACTCCCTAT DSYQNRLFYTLKTGETVAD QAPGKEREFVSGIS CAGTGATAGA LSKSQDINLSTIWSLNKHLY WRGDSTGYADSV GAA (SEQ ID SSESEMMKAAPGQQIILPL KGRFTISRDNAKN NO: 1488) KKLPFEYSALPLLGSAPLV TVDLQMNSLKPED AAGGVAGHTNKLTKMSPD TAIYYCAAAAGSA VTKSNMTDDKALNYAAQQ WYGTLYEYDYWG AASLGSQLQSRSLNGDYAK QGTQVTVSS DTALGIAGNQASSQLQAW (SEQ ID NO: LQHYGTAEVNLQSGNNFD 1511) GSSLDFLLPFYDSEKMLAF GQVGARYIDSRFTANLGAG QRFFLPANMLGYNVFIDQD FSGDNTRLGIGGEYWRDYF KSSVNGYFRMSGWHESYN KKDYDERPANGFDIRFNGY LPSYPALGAKLIYEQYYGD NVALFNSDKLQSNPGAAT VGVNYTPIPLVTMGIDYRH GTGNENDLLYSMQFRYQF DKSWSQQIEPQYVNELRTL SGSRYDLVQRNNNIILEYK KQDILSLNIPHDINGTEHST QKIQLIVKSKYGLDRIVWD DSALRSQGGQIQHSGSQSA QDYQAILPAYVQGGSNIYK VTARAYDRNGNSSNNVQL TITVLSNGQVVDQVGVTDF TADKTSAKADNADTITYTA TVKKNGVAQANVPVSFNIV SGTATLGANSAKTDANGK ATVTLKSSTPGQVVVSAKT AEMTSALNASAVIFFDQTK AS (SEQ ID NO: 1501) SYN7192 FLAG- GTTGACACTCT MITHGCYTRTRHKHKLKK AQVKLEESGGGSV aEGFR4- ATCATTGATA TLIMLSAGLGLFFYVNQNS QTGGSLRLTCAAS His-myc GAGTTATTTTA FANGENYFKLGSDSKLLTH GRTSRSYGMGWF CCACTCCCTAT DSYQNRLFYTLKTGETVAD RQAPGKEREFVSG CAGTGATAGA LSKSQDINLSTIWSLNKHLY ISWRGDSTGYADS GAA SSESEMMKAAPGQQIILPL VKGRFTISRDNAK (SEQ ID KKLPFEYSALPLLGSAPLV NTVDLQMNSLKPE NO: 1488) AAGGVAGHTNKLTKMSPD DTAIYYCAAAAGS VTKSNMTDDKALNYAAQQ AWYGTLYEYDYW AASLGSQLQSRSLNGDYAK GQGTQVTVSSSPS DTALGIAGNQASSQLQAW TPPTPSPSTPPGLN LQHYGTAEVNLQSGNNFD DIFEAQKIEWHGS GSSLDFLLPFYDSEKMLAF S GQVGARYIDSRFTANLGAG (SEQ ID QRFFLPANMLGYNVFIDQD NO: FSGDNTRLGIGGEYWRDYF 1504) KSSVNGYFRMSGWHESYN KKDYDERPANGFDIRFNGY LPSYPALGAKLIYEQYYGD NVALFNSDKLQSNPGAAT VGVNYTPIPLVTMGIDYRH GTGNENDLLYSMQFRYQF DKSWSQQIEPQYVNELRTL SGSRYDLVQRNNNIILEYK KQDILSLNIPHDINGTEHST QKIQLIVKSKYGLDRIVWD DSALRSQGGQIQHSGSQSA QDYQAILPAYVQGGSNIYK VTARAYDRNGNSSNNVQL TITVLSNGQVVDQVGVTDF TADKTSAKADNADTITYTA TVKKNGVAQANVPVSFNIV SGTATLGANSAKTDANGK ATVTLKSSTPGQVVVSAKT AEMTSALNASAVIFFDQTK AS (SEQ ID NO: 1501)

Example 3. Development of Vaccine for Prevention of COVID19

[0516] Coronaviruses (CoV) are a large family of viruses that cause diseases in mammals and birds. Coronaviruses constitute the subfamily Orthocoronavirinae, in the family Coronaviridae. They are enveloped viruses with a positive-sense single-stranded RNA genome and a nucleocapsid of helical symmetry. The genome size of coronaviruses ranges from approximately 27 to 34 kilobases. The name coronavirus is derived from the Latin corona, meaning "crown" or "halo", which refers to the characteristic appearance reminiscent of a crown or a solar corona around the virions (virus particles) when viewed under two-dimensional transmission electron microscopy, due to the surface covering in club-shaped protein spikes.

[0517] Coronaviruses can cause illness ranging from the common cold to more severe diseases. For example, infections with the human coronavirus strains CoV-229E, CoV-OC43, CoV-NL63 and CoV-HKU1 usually result in mild, self-limiting upper respiratory tract infections, such as a common cold, e.g., runny nose, sneezing, headache, cough, sore throat or fever (Zumla A. et al., Nature Reviews Drug Discovery 15(5): 327-47, 2016; (Cheng V. C., et al., Clin. Microbial. Rev. 20: 660-694, 2007; Chan J. F. et al., Clin. Microbial. Rev. 28: 465-522, 2015). Other infections may result in more severe diseases such as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV), diseases associated with pneumonia, severe acute respiratory syndrome, kidney failure and death.

[0518] MERS-CoV and SARS-CoV have received global attention over the past decades owing to their ability to cause community and health-care-associated outbreaks of severe infections in human populations. MERS-CoV is a viral respiratory disease that was first reported in Saudi Arabia in 2012 and has since spread to more than 27 other countries, according to the World Health Organization (de Groot, R. J. et al., J. Virol. 87: 7790-7792, 2013). SARS was first reported in Asia in 2003, and quickly spread to about two dozen countries before being contained after about four months (Lee N. et al., N. Engl. J. Med. 348: 1986-1994, 2003; Peiris J. S. et al., Lancet 36: 1319-1325, 2003). Detailed investigations found that SARS-CoV was transmitted from civet cats to humans and MERS-CoV from dromedary camels to humans (Cheng V. C., et al., Clin. Microbial. Rev. 20: 660-694, 2007; Chan J. F. et al., Clin. Microbial. Rev. 28: 465-522, 2015).

[0519] A recent outbreak of respiratory disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan City, China. This disease, named by the World Health Organization as coronavirus disease 2019 ("COVID-19"), presents a major threat to public health worldwide.

[0520] Coronaviruses viruses pose major challenges to clinical management because many questions regarding transmission and control remain unanswered. Moreover, there is currently no vaccine to prevent infections by coronavirus, and there are no specific antiviral treatments available or proven to be effective to treat or prevent coronavirus infection in subjects.

[0521] The capsid spike (S) protein of SARS-CoV2 virus initiates attachment to the angiotensin converting enzyme 2 (ACE2) receptor expressed on the surface of human epithelial cells, facilitating viral entry. The receptor binding domain (RBD) region of the spike protein interacts directly with the ACE2 receptor. Neutralizing antibodies directed against S protein have been observed in patients that have recovered from COVID-19, making S protein and its RBD region an attractive target for vaccine development.

[0522] A vaccine for the prevention of COVID19 (or SARS-CoV2) is developed by utilizing synthetic biology techniques to engineer probiotic bacteria that express viral proteins (S-protein RBD) and immune activators/adjuvants. This vaccine is based on an engineered E. coli Nissle (EcN) bacterial strain that expresses viral spike protein receptor bindind domain (RBD) from SARS-CoV2, the causative agent for COVID-19 on its cell surface, and can be administered intranasally to induce protective immunity systemically and at mucosal surfaces.

[0523] Specifically, SYNB1891, a clinical candidate for anti-tumor immunity currently in phase I clinical trials, is used as a starting point for engineering. This strain is designed to stimulate the immune system by producing immune activators/adjuvants.

[0524] To successfully generate neutralizing antibodies against the RBD region of SARS-CoV2 spike protein, it is essential that the RBD region expressed and displayed on the surface of EcN be conformationally similar to the native RBD region found on SARS-CoV2 spike protein. Even a slight change in the folding and conformation of RBD region on the surface of EcN can lead to the generation of antibodies that are not efficacious against neutralizing the virus. In addition, since spike protein is a glycosylated protein and EcN expresses proteins that are un-glycosylated, this has the potential to impact the conformation and therefore of efficacy of the generated antibody response against SARS CoV-2. Therefore, to minimize the risk of conformational dissimilarity, a bioinformatics approach is employed to perform a structural analysis of the RBD region and a library of RBD expression constructs is designed with construct having varying sizes of flanking sequences on either side to maximize the probability of correct folding.

[0525] A genomic library of RBD constructs containing linker regions of various lengths, fused to an appropriate outer membrane-anchoring domain is generated. Several potential anchoring domains were identified to facilitate the delivery of protein to the cell service. The RBD construct libraries are fused to the top 3 anchoring domains. To assess proper display on the cell surface, a high throughput assay is developed. Briefly, a structurally-specific .alpha.-RBD antibody (with conjugated fluorophore) is used to stain cells expressing members of the RBD library. Whole cells that acquire fluorescence indicate that the antibody has successfully bound to the cell surface, which also indicates that the RBD library member is likely to be expressed in a conformationally relevant manner. Additionally, RBD constructs may adopt the native trimeric structure on the cell surface, so a secondary assay using recombinant ACE2 protein followed by staining with fluorophore-conjugated .alpha.-ACE2 antibody can also be attempted as a secondary screen.

[0526] Viral sensing by innate immune cells triggers various signaling cascades including Stimulator of Interferon Genes (STING), leading to the production of interferons and proinflammatory cytokines critical for induction of effective innate and adaptive anti-viral immunity (Lee, H., et al., 2019. Exp Mol Med 51, 1-13). The engineered bacterial strain SYNB1891 produces the STING agonist that triggers STING activation and Type I interferon production in antigen-presenting cells leading to the induction of tumor antigen-specific cytotoxic T-cell responses, and in preclinical models, efficacious antitumor immunity with the formation of immunological memory. SYNB1891 could be further engineered to induce antigen-specific mucosal and systemic immunity to SARS-CoV2.

[0527] SYNB medicines are well suited to advance an engineered bacterial product as a vaccine candidate for COVID-19. In particular, the EcN based vaccine confers several advantages when compared to the current anti-viral vaccine approaches as described below and shown in FIG. 10. The EcN based vaccine displays a protein to induce an immune response, contains STING agonist, and is unable to proliferate.

[0528] Efficacy: Rationally designed, specific viral proteins and immune activators as well as additional functionalities can be engineered into a single cell to induce a protein specific mucosal and systemic immune response. The bacterial chassis itself provides adjuvant effects and allows direct uptake of concentrated protein and activator by antigen presenting cells.

[0529] Safety: EcN has been used orally in human populations for over 100 years with a very good safety profile. EcN exhibits serum sensitivity to complement lysis and is susceptible to a broad array of antibiotics. The safety profile of EcN delivered intranasally should be similar. The vaccine of the present invention contains no live virus, and is delivered locally, so has the potential for a safety advantage over attenuated or recombinant viral and DNA vaccine approaches. Prevention of cell division using auxotrophies is engineered to avoid any uncontrolled bacterial growth in the body or the environment. The prototype, SYNB1891 injected intratumorally is now being evaluated in a clinical trial NCT04167137, providing additional human safety data.

[0530] Manufacturability: 6 million doses of vaccine can be produced in a single batch (at a dose level of 1.times.10.sup.9 live cells/dose).

[0531] Stability: SYNB lyophilized cells have room temperature stability for stockpiling. The vaccine would have to be lyophilized for adequate stockpiling and long term stability. There is a risk that the outer membrane of the bacteria is damaged during the lyophilization process, which could have the effect of damaging or denaturing surface-displayed components.

[0532] Therefore, the advancement over current anti-viral vaccine approaches is the integration of multiple desired features into a single organism to produce a vaccine with enhanced safety and specific immunity to viral proteins. Additionally, the technology is scalable to manufacture large quantities of vaccine.

Technical Section:

[0533] The existing strain, SYNB1891, is engineered to express the conformationally stable spike protein (S-protein, receptor binding domain) of SARS-CoV2, a critical means of entry of the virus into respiratory cells and a target for other coronavirus vaccine initiatives (Du L., et al, 2019 Exp Mol Med 51, 1-13; Wan Y., et al., 2009 Nat Rev Microbiol. 7(3): 226-236; Wan Y., et al., 2020 J Virol 94: e00127-20; Chen W., et al., 2020. Current Tropical Medicine Reports. https://doi.org/10.1007/s40475-020-00201-6; Kirchdoerfer R, et al., 2018. Scientific Reports; 8:15701). The strain is designed for the local intranasal delivery to enhance mucosal immunity in the respiratory tract where it will mimic natural entry of SARS-CoV2.

[0534] In other embodiments, the existing strain, SYNB1891, is engineered to express a epitope which induces a CTL response. In one embodiment, the epitope is in the viral nucleocapsid (N) and/or M protein. Such proteins and epitopes are well known in the art and described at least in Liu et al., Antiviral Research 137 (2017), 82-92; Huang et al., Vaccine 25 (2007):6981-6991; Ahmed et al., Viruses (2020) 12:254; Grifoni et al., Cell Host & Microbiome (2020) 27:1-10; and Chen et al., J. Immunol (2005) 175:591-598, the entire contents of each of which are expressly incorporated by reference herein in their entireties.

[0535] A clinical candidate strain that produces a STING Agonist has been engineered. Specifically, a strain of EcN, called SYNB1891, was engineered to produce the STING agonist, c-di-AMP, in the microenvironment by expressing the dacA gene from Listeria monocytogenes under the control of an inducible promoter. SYNB1891 serves as the background strain for further COVID19 vaccine development.

[0536] Biologically active proteins can be displayed on the EcN cell surface. The display of proteins on the E. coli surface has been previously described in the literature (Van Bloois E, et al, 2011. Trends Biotechnol. 29(2):79-86).

[0537] SYNB1891 has been demonstrated to induce innate and adaptive immune responses. SYNB1891 mechanisms of action include upregulation of 2 innate immune axes: [1] direct STING activation by c-di-AMP and [2] activation of other pattern recognition receptors (including TLR4) by the bacterial chassis itself. SYNB1891 was able to induce Type I IFNs and proinflammatory cytokines from mouse and human dendritic cells and locally in the tumor. The ability of SYNB1891 to induce Type I IFNs in addition to proinflammatory cytokines led to the development of functional anti-tumor CD8+ T cells and immunological memory. These data demonstrate that SYNB1891 triggers relevant innate immune pathways that lead to antigen-specific activation of CD8+ T cell response. Since SYNB1891 mechanisms of action are similarly important for the development of protective anti-viral immunity, these data validate the use of SYNB1891 as a strain to express the SARS-CoV2 protein.

[0538] Safety has been engineered directly applicable to a potential vaccine candidate. From a safety and regulatory perspective, biocontainment controls are critical elements of a bacterial-based live therapeutic designed for clinical use. The EcN chassis itself shows serum sensitivity (Grozdanov L, et al., 2002, J Bacteriol; 184:5912-25), antibiotic sensitivity and unable to colonize human gut. Yet, engineered Thymidine (thy) and Diaminopimelic acid (dap) auxotrophies, implemented in SYNB1891 led to inability of this bacterial strain to colonize and proliferate even in immuno-privileged tumor environment. SYNB1891-specific qPCR showed low or absent bacterial biodistribution outside of site of injection.

[0539] Bacterial vaccines are not a new concept. There are approved live bacterial vaccines (i.e. for cholera) as well as vaccines being explored in clinical trials and preclinically (Ming Zeng, et al., 2015. Lancet; 386: 1457-64; Thorstensson R, et al., 2014. PLoS ONE 9(1): e83449; Pei-Feng Liu, et al. 2017. Nat Sci. 3(2): e317; Nathalie Mielcarek et al. 2001. Advanced Drug Delivery Reviews 51: 55-69; Adilson Jose da Silva, et al. 2014. Brazilian Journal of Microbiology 45, 4, 1117-1129). However, induction of an immune response to SARS-CoV2 by any vaccine could generate antibodies that may potentiate immunopathology during infection. This present application also include studies to evaluate both efficacy and safety of the vaccine in at least 2 species (rodent and non-rodent) in the context of a live viral infection with SARS-CoV2.

Ability to Transition Technology and Expand Use

[0540] Probiotic EcN strains have been engineered for the treatment of metabolic diseases, immunologic diseases, and cancer, and have been tested in Phase 1/2 clinical trials, in healthy volunteers as well as in patients. Multiple doses of vaccine under cGMP can be manufactured for human use. The manufacturing capabilities currently allow for cGMP production of batch sizes of up to 300L, in both liquid and solid presentations. Numerous batches are ran throughout the year to support high level of demands. These core competencies of genetic engineering, clinical development and manufacturing provide the ability to deploy a validated platform for the development and production of a COVID-19 vaccine. Additionally, the technology developed here for a COVID-19 vaccine could be readily deployed for other respiratory viruses.

[0541] Task 1. Engineering: The current SYNB1891 strain (expressing STING agonist c-di-AMP, double auxotrophy) is engineered to express the SARS-CoV2 Spike-protein Receptor Binding Domain (S-protein RBD).

[0542] Steps:

[0543] 1. Design, build and transform plasmids containing expression cassettes for S-protein with various arrangements (e.g. RBD region only, tandem design, or fusion proteins) targeted for EcN surface display.

[0544] 2. Demonstrate expression of protein on the surface of EcN in vitro, in a biologically active conformation.

[0545] 3. Demonstrate the production of c-di-AMP along with protein display on the surface of EcN SYNB1891 strain carrying plasmids described above.

[0546] 4. Integrate key genetic elements into the chromosome of EcN SYNB1891 and demonstrate the production of c-di-AMP and surface display of protein in final integrated strain in vitro.

[0547] An EcN strain with genetic circuits designed for the production of c-di-AMP production as well as surface display of protein of S-protein (or variants thereof) in a biologically relevant conformation. The strain will also be engineered to contain a dual auxotrophy for diaminopimelic acid and thymidine, to inhibit replication in vivo and for biocontainment.

[0548] Task 2. Initial in vivo characterization: Characterize engineered SARS-CoV2-S protein expressing strains delivered intranasally to mice by evaluating initial tolerability, residence time and generation of S-antigen specific immune responses. Additionally explore oral route of vaccine delivery.

[0549] Steps:

[0550] 1. Develop all necessary assays to evaluate in vivo antibody and T cell responses.

[0551] 2. Demonstrate strain viability and residence time at the target mucosal surfaces.

[0552] 3. Evaluate distribution of live strain in upper respiratory tract, lungs, GI tract and blood. Assess initial mouse tolerability to the treatment/route of administration.

[0553] 4. Demonstrate generation of protein-specific antibodies in the lungs (target organ), GI tract and blood of Balb/c and C57BL/6 mice after immunization. Characterize type of antibody response, e.g., IgA, IgGs, IgE.

[0554] 5. Demonstrate generation and characterize protein-specific T cell responses, e.g., CD4+ Th1/Th2 ratio, CD8+ T cell activation.

[0555] Demonstrate generation of protein-specific antiviral T cell responses (mostly protective CD4+Th1 and CD8+ T cells without overactivation/skewing to Th2- cell response). Demonstrate anti-viral antibody production (mucosal and systemic) in the immunized mice. Select engineered SARS-CoV2-S protein expressing strain and route of vaccine administration for further evaluation.

[0556] Task 3. Efficacy: Test development of protective immunity and neutralizing antibody responses. This work will require collaboration with a BSL3 laboratory capable of infecting a sensitive mouse strain with SARS-CoV2.

[0557] Steps:

[0558] 1. Viral neutralization: Test ability of serum and mucosal antibody to neutralize and prevent infection of human lung epithelial cells with SARS-CoV2.

[0559] 2. Anti-viral CTL response: Test ability of CD8+ T cells to kill mouse hACE2+ lung epithelial cells infected with SARS-CoV2 or mouse epithelial cells expressing viral S protein.

[0560] 3. Demonstrate generation of protein-specific IgA/IgG antibodies in the lungs (target organ) and blood after immunization of K18-hACE2 transgenic mouse model (18) (or another mouse model susceptible to SARS CoV2) adopted for COVID-19 research. Additional models like ferrets and NHPs will also be considered.

[0561] 4. Demonstrate generation of protective immune response and survival of immunized K18-hACE2 transgenic mouse (or other SARS-CoV2 model) after infection with a lethal dose of SARs-CoV2.

[0562] Task 4. Safety: Evaluate safety of engineered SARS-CoV2-S protein expressing strain in vivo. Part of this work will require collaboration with a BSL3 laboratory capable of infecting a sensitive mouse strain with SARS-CoV2.

[0563] Steps:

[0564] 1. Toxicology studies to test bacterial spread in blood and multiple organs (especially lungs and brain) by sensitive strain-specific qPCR.

[0565] 2. Examine systemic pro-inflammatory cytokine release e.g. IL-6, TNF.alpha. etc. after immunization.

[0566] 3. Evaluate undesired antibody-dependent enhancement of immunopathogenesis: increase of viral uptake through opsonizing antibody and overactivation of macrophages, B cells and DCs, resulting in disease enhancement and viral dissemination.

[0567] 4. Evaluate occurrence of Th2-type eosinophilic lung inflammation in immunized animals following SARS-CoV2 challenge.

Sequence CWU 1 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 1511 <210> SEQ ID NO 1 <400> SEQUENCE: 1 000 <210> SEQ ID NO 2 <400> SEQUENCE: 2 000 <210> SEQ ID NO 3 <400> SEQUENCE: 3 000 <210> SEQ ID NO 4 <400> SEQUENCE: 4 000 <210> SEQ ID NO 5 <400> SEQUENCE: 5 000 <210> SEQ ID NO 6 <400> SEQUENCE: 6 000 <210> SEQ ID NO 7 <400> SEQUENCE: 7 000 <210> SEQ ID NO 8 <400> SEQUENCE: 8 000 <210> SEQ ID NO 9 <400> SEQUENCE: 9 000 <210> SEQ ID NO 10 <400> SEQUENCE: 10 000 <210> SEQ ID NO 11 <400> SEQUENCE: 11 000 <210> SEQ ID NO 12 <400> SEQUENCE: 12 000 <210> SEQ ID NO 13 <400> SEQUENCE: 13 000 <210> SEQ ID NO 14 <400> SEQUENCE: 14 000 <210> SEQ ID NO 15 <400> SEQUENCE: 15 000 <210> SEQ ID NO 16 <400> SEQUENCE: 16 000 <210> SEQ ID NO 17 <400> SEQUENCE: 17 000 <210> SEQ ID NO 18 <400> SEQUENCE: 18 000 <210> SEQ ID NO 19 <400> SEQUENCE: 19 000 <210> SEQ ID NO 20 <400> SEQUENCE: 20 000 <210> SEQ ID NO 21 <400> SEQUENCE: 21 000 <210> SEQ ID NO 22 <400> SEQUENCE: 22 000 <210> SEQ ID NO 23 <400> SEQUENCE: 23 000 <210> SEQ ID NO 24 <400> SEQUENCE: 24 000 <210> SEQ ID NO 25 <400> SEQUENCE: 25 000 <210> SEQ ID NO 26 <400> SEQUENCE: 26 000 <210> SEQ ID NO 27 <400> SEQUENCE: 27 000 <210> SEQ ID NO 28 <400> SEQUENCE: 28 000 <210> SEQ ID NO 29 <400> SEQUENCE: 29 000 <210> SEQ ID NO 30 <400> SEQUENCE: 30 000 <210> SEQ ID NO 31 <400> SEQUENCE: 31 000 <210> SEQ ID NO 32 <400> SEQUENCE: 32 000 <210> SEQ ID NO 33 <400> SEQUENCE: 33 000 <210> SEQ ID NO 34 <400> SEQUENCE: 34 000 <210> SEQ ID NO 35 <400> SEQUENCE: 35 000 <210> SEQ ID NO 36 <400> SEQUENCE: 36 000 <210> SEQ ID NO 37 <400> SEQUENCE: 37 000 <210> SEQ ID NO 38 <400> SEQUENCE: 38 000 <210> SEQ ID NO 39 <400> SEQUENCE: 39 000 <210> SEQ ID NO 40 <400> SEQUENCE: 40 000 <210> SEQ ID NO 41 <400> SEQUENCE: 41 000 <210> SEQ ID NO 42 <400> SEQUENCE: 42 000 <210> SEQ ID NO 43 <400> SEQUENCE: 43 000 <210> SEQ ID NO 44 <400> SEQUENCE: 44 000 <210> SEQ ID NO 45 <400> SEQUENCE: 45 000 <210> SEQ ID NO 46 <400> SEQUENCE: 46 000 <210> SEQ ID NO 47 <400> SEQUENCE: 47 000 <210> SEQ ID NO 48 <400> SEQUENCE: 48 000 <210> SEQ ID NO 49 <400> SEQUENCE: 49 000 <210> SEQ ID NO 50 <400> SEQUENCE: 50 000 <210> SEQ ID NO 51 <400> SEQUENCE: 51 000 <210> SEQ ID NO 52 <400> SEQUENCE: 52 000 <210> SEQ ID NO 53 <400> SEQUENCE: 53 000 <210> SEQ ID NO 54 <400> SEQUENCE: 54 000 <210> SEQ ID NO 55 <400> SEQUENCE: 55 000 <210> SEQ ID NO 56 <400> SEQUENCE: 56 000 <210> SEQ ID NO 57 <400> SEQUENCE: 57 000 <210> SEQ ID NO 58 <400> SEQUENCE: 58 000 <210> SEQ ID NO 59 <400> SEQUENCE: 59 000 <210> SEQ ID NO 60 <400> SEQUENCE: 60 000 <210> SEQ ID NO 61 <400> SEQUENCE: 61 000 <210> SEQ ID NO 62 <400> SEQUENCE: 62 000 <210> SEQ ID NO 63 <400> SEQUENCE: 63 000 <210> SEQ ID NO 64 <400> SEQUENCE: 64 000 <210> SEQ ID NO 65 <400> SEQUENCE: 65 000 <210> SEQ ID NO 66 <400> SEQUENCE: 66 000 <210> SEQ ID NO 67 <400> SEQUENCE: 67 000 <210> SEQ ID NO 68 <400> SEQUENCE: 68 000 <210> SEQ ID NO 69 <400> SEQUENCE: 69 000 <210> SEQ ID NO 70 <400> SEQUENCE: 70 000 <210> SEQ ID NO 71 <400> SEQUENCE: 71 000 <210> SEQ ID NO 72 <400> SEQUENCE: 72 000 <210> SEQ ID NO 73 <400> SEQUENCE: 73 000 <210> SEQ ID NO 74 <400> SEQUENCE: 74 000 <210> SEQ ID NO 75 <400> SEQUENCE: 75 000 <210> SEQ ID NO 76 <400> SEQUENCE: 76 000 <210> SEQ ID NO 77 <400> SEQUENCE: 77 000 <210> SEQ ID NO 78 <400> SEQUENCE: 78 000 <210> SEQ ID NO 79 <400> SEQUENCE: 79 000 <210> SEQ ID NO 80 <400> SEQUENCE: 80 000 <210> SEQ ID NO 81 <400> SEQUENCE: 81 000 <210> SEQ ID NO 82 <400> SEQUENCE: 82 000 <210> SEQ ID NO 83 <400> SEQUENCE: 83 000 <210> SEQ ID NO 84 <400> SEQUENCE: 84 000 <210> SEQ ID NO 85 <400> SEQUENCE: 85 000 <210> SEQ ID NO 86 <400> SEQUENCE: 86 000 <210> SEQ ID NO 87 <400> SEQUENCE: 87 000 <210> SEQ ID NO 88 <400> SEQUENCE: 88 000 <210> SEQ ID NO 89 <400> SEQUENCE: 89 000 <210> SEQ ID NO 90 <400> SEQUENCE: 90 000 <210> SEQ ID NO 91 <400> SEQUENCE: 91 000 <210> SEQ ID NO 92 <400> SEQUENCE: 92 000 <210> SEQ ID NO 93 <400> SEQUENCE: 93 000 <210> SEQ ID NO 94 <400> SEQUENCE: 94 000 <210> SEQ ID NO 95 <400> SEQUENCE: 95 000 <210> SEQ ID NO 96 <400> SEQUENCE: 96 000 <210> SEQ ID NO 97 <400> SEQUENCE: 97 000 <210> SEQ ID NO 98 <400> SEQUENCE: 98 000 <210> SEQ ID NO 99 <400> SEQUENCE: 99 000 <210> SEQ ID NO 100 <400> SEQUENCE: 100 000 <210> SEQ ID NO 101 <400> SEQUENCE: 101 000 <210> SEQ ID NO 102 <400> SEQUENCE: 102 000 <210> SEQ ID NO 103 <400> SEQUENCE: 103 000 <210> SEQ ID NO 104 <400> SEQUENCE: 104 000 <210> SEQ ID NO 105 <400> SEQUENCE: 105 000 <210> SEQ ID NO 106 <400> SEQUENCE: 106 000 <210> SEQ ID NO 107 <400> SEQUENCE: 107 000 <210> SEQ ID NO 108 <400> SEQUENCE: 108 000 <210> SEQ ID NO 109 <400> SEQUENCE: 109 000 <210> SEQ ID NO 110 <400> SEQUENCE: 110 000 <210> SEQ ID NO 111 <400> SEQUENCE: 111 000 <210> SEQ ID NO 112 <400> SEQUENCE: 112 000 <210> SEQ ID NO 113 <400> SEQUENCE: 113 000 <210> SEQ ID NO 114 <400> SEQUENCE: 114 000 <210> SEQ ID NO 115 <400> SEQUENCE: 115 000 <210> SEQ ID NO 116 <400> SEQUENCE: 116 000 <210> SEQ ID NO 117 <400> SEQUENCE: 117 000 <210> SEQ ID NO 118 <400> SEQUENCE: 118 000 <210> SEQ ID NO 119 <400> SEQUENCE: 119 000 <210> SEQ ID NO 120 <400> SEQUENCE: 120 000 <210> SEQ ID NO 121 <400> SEQUENCE: 121 000 <210> SEQ ID NO 122 <400> SEQUENCE: 122 000 <210> SEQ ID NO 123 <400> SEQUENCE: 123 000 <210> SEQ ID NO 124 <400> SEQUENCE: 124 000 <210> SEQ ID NO 125 <400> SEQUENCE: 125 000 <210> SEQ ID NO 126 <400> SEQUENCE: 126 000 <210> SEQ ID NO 127 <400> SEQUENCE: 127 000 <210> SEQ ID NO 128 <400> SEQUENCE: 128 000 <210> SEQ ID NO 129 <400> SEQUENCE: 129 000 <210> SEQ ID NO 130 <400> SEQUENCE: 130 000 <210> SEQ ID NO 131 <400> SEQUENCE: 131 000 <210> SEQ ID NO 132 <400> SEQUENCE: 132 000 <210> SEQ ID NO 133 <400> SEQUENCE: 133 000 <210> SEQ ID NO 134 <400> SEQUENCE: 134 000 <210> SEQ ID NO 135 <400> SEQUENCE: 135 000 <210> SEQ ID NO 136 <400> SEQUENCE: 136 000 <210> SEQ ID NO 137 <400> SEQUENCE: 137 000 <210> SEQ ID NO 138 <400> SEQUENCE: 138 000 <210> SEQ ID NO 139 <400> SEQUENCE: 139 000 <210> SEQ ID NO 140 <400> SEQUENCE: 140 000 <210> SEQ ID NO 141 <400> SEQUENCE: 141 000 <210> SEQ ID NO 142 <400> SEQUENCE: 142 000 <210> SEQ ID NO 143 <400> SEQUENCE: 143 000 <210> SEQ ID NO 144 <400> SEQUENCE: 144 000 <210> SEQ ID NO 145 <400> SEQUENCE: 145 000 <210> SEQ ID NO 146 <400> SEQUENCE: 146 000 <210> SEQ ID NO 147 <400> SEQUENCE: 147 000 <210> SEQ ID NO 148 <400> SEQUENCE: 148 000 <210> SEQ ID NO 149 <400> SEQUENCE: 149 000 <210> SEQ ID NO 150 <400> SEQUENCE: 150 000 <210> SEQ ID NO 151 <400> SEQUENCE: 151 000 <210> SEQ ID NO 152 <400> SEQUENCE: 152 000 <210> SEQ ID NO 153 <400> SEQUENCE: 153 000 <210> SEQ ID NO 154 <400> SEQUENCE: 154 000 <210> SEQ ID NO 155 <400> SEQUENCE: 155 000 <210> SEQ ID NO 156 <400> SEQUENCE: 156 000 <210> SEQ ID NO 157 <400> SEQUENCE: 157 000 <210> SEQ ID NO 158 <400> SEQUENCE: 158 000 <210> SEQ ID NO 159 <400> SEQUENCE: 159 000 <210> SEQ ID NO 160 <400> SEQUENCE: 160 000 <210> SEQ ID NO 161 <400> SEQUENCE: 161 000 <210> SEQ ID NO 162 <400> SEQUENCE: 162 000 <210> SEQ ID NO 163 <400> SEQUENCE: 163 000 <210> SEQ ID NO 164 <400> SEQUENCE: 164 000 <210> SEQ ID NO 165 <400> SEQUENCE: 165 000 <210> SEQ ID NO 166 <400> SEQUENCE: 166 000 <210> SEQ ID NO 167 <400> SEQUENCE: 167 000 <210> SEQ ID NO 168 <400> SEQUENCE: 168 000 <210> SEQ ID NO 169 <400> SEQUENCE: 169 000 <210> SEQ ID NO 170 <400> SEQUENCE: 170 000 <210> SEQ ID NO 171 <400> SEQUENCE: 171 000 <210> SEQ ID NO 172 <400> SEQUENCE: 172 000 <210> SEQ ID NO 173 <400> SEQUENCE: 173 000 <210> SEQ ID NO 174 <400> SEQUENCE: 174 000 <210> SEQ ID NO 175 <400> SEQUENCE: 175 000 <210> SEQ ID NO 176 <400> SEQUENCE: 176 000 <210> SEQ ID NO 177 <400> SEQUENCE: 177 000 <210> SEQ ID NO 178 <400> SEQUENCE: 178 000 <210> SEQ ID NO 179 <400> SEQUENCE: 179 000 <210> SEQ ID NO 180 <400> SEQUENCE: 180 000 <210> SEQ ID NO 181 <400> SEQUENCE: 181 000 <210> SEQ ID NO 182 <400> SEQUENCE: 182 000 <210> SEQ ID NO 183 <400> SEQUENCE: 183 000 <210> SEQ ID NO 184 <400> SEQUENCE: 184 000 <210> SEQ ID NO 185 <400> SEQUENCE: 185 000 <210> SEQ ID NO 186 <400> SEQUENCE: 186 000 <210> SEQ ID NO 187 <400> SEQUENCE: 187 000 <210> SEQ ID NO 188 <400> SEQUENCE: 188 000 <210> SEQ ID NO 189 <400> SEQUENCE: 189 000 <210> SEQ ID NO 190 <400> SEQUENCE: 190 000 <210> SEQ ID NO 191 <400> SEQUENCE: 191 000 <210> SEQ ID NO 192 <400> SEQUENCE: 192 000 <210> SEQ ID NO 193 <400> SEQUENCE: 193 000 <210> SEQ ID NO 194 <400> SEQUENCE: 194 000 <210> SEQ ID NO 195 <400> SEQUENCE: 195 000 <210> SEQ ID NO 196 <400> SEQUENCE: 196 000 <210> SEQ ID NO 197 <400> SEQUENCE: 197 000 <210> SEQ ID NO 198 <400> SEQUENCE: 198 000 <210> SEQ ID NO 199 <400> SEQUENCE: 199 000 <210> SEQ ID NO 200 <400> SEQUENCE: 200 000 <210> SEQ ID NO 201 <400> SEQUENCE: 201 000 <210> SEQ ID NO 202 <400> SEQUENCE: 202 000 <210> SEQ ID NO 203 <400> SEQUENCE: 203 000 <210> SEQ ID NO 204 <400> SEQUENCE: 204 000 <210> SEQ ID NO 205 <400> SEQUENCE: 205 000 <210> SEQ ID NO 206 <400> SEQUENCE: 206 000 <210> SEQ ID NO 207 <400> SEQUENCE: 207 000 <210> SEQ ID NO 208 <400> SEQUENCE: 208 000 <210> SEQ ID NO 209 <400> SEQUENCE: 209 000 <210> SEQ ID NO 210 <400> SEQUENCE: 210 000 <210> SEQ ID NO 211 <400> SEQUENCE: 211 000 <210> SEQ ID NO 212 <400> SEQUENCE: 212 000 <210> SEQ ID NO 213 <400> SEQUENCE: 213 000 <210> SEQ ID NO 214 <400> SEQUENCE: 214 000 <210> SEQ ID NO 215 <400> SEQUENCE: 215 000 <210> SEQ ID NO 216 <400> SEQUENCE: 216 000 <210> SEQ ID NO 217 <400> SEQUENCE: 217 000 <210> SEQ ID NO 218 <400> SEQUENCE: 218 000 <210> SEQ ID NO 219 <400> SEQUENCE: 219 000 <210> SEQ ID NO 220 <400> SEQUENCE: 220 000 <210> SEQ ID NO 221 <400> SEQUENCE: 221 000 <210> SEQ ID NO 222 <400> SEQUENCE: 222 000 <210> SEQ ID NO 223 <400> SEQUENCE: 223 000 <210> SEQ ID NO 224 <400> SEQUENCE: 224 000 <210> SEQ ID NO 225 <400> SEQUENCE: 225 000 <210> SEQ ID NO 226 <400> SEQUENCE: 226 000 <210> SEQ ID NO 227 <400> SEQUENCE: 227 000 <210> SEQ ID NO 228 <400> SEQUENCE: 228 000 <210> SEQ ID NO 229 <400> SEQUENCE: 229 000 <210> SEQ ID NO 230 <400> SEQUENCE: 230 000 <210> SEQ ID NO 231 <400> SEQUENCE: 231 000 <210> SEQ ID NO 232 <400> SEQUENCE: 232 000 <210> SEQ ID NO 233 <400> SEQUENCE: 233 000 <210> SEQ ID NO 234 <400> SEQUENCE: 234 000 <210> SEQ ID NO 235 <400> SEQUENCE: 235 000 <210> SEQ ID NO 236 <400> SEQUENCE: 236 000 <210> SEQ ID NO 237 <400> SEQUENCE: 237 000 <210> SEQ ID NO 238 <400> SEQUENCE: 238 000 <210> SEQ ID NO 239 <400> SEQUENCE: 239 000 <210> SEQ ID NO 240 <400> SEQUENCE: 240 000 <210> SEQ ID NO 241 <400> SEQUENCE: 241 000 <210> SEQ ID NO 242 <400> SEQUENCE: 242 000 <210> SEQ ID NO 243 <400> SEQUENCE: 243 000 <210> SEQ ID NO 244 <400> SEQUENCE: 244 000 <210> SEQ ID NO 245 <400> SEQUENCE: 245 000 <210> SEQ ID NO 246 <400> SEQUENCE: 246 000 <210> SEQ ID NO 247 <400> SEQUENCE: 247 000 <210> SEQ ID NO 248 <400> SEQUENCE: 248 000 <210> SEQ ID NO 249 <400> SEQUENCE: 249 000 <210> SEQ ID NO 250 <400> SEQUENCE: 250 000 <210> SEQ ID NO 251 <400> SEQUENCE: 251 000 <210> SEQ ID NO 252 <400> SEQUENCE: 252 000 <210> SEQ ID NO 253 <400> SEQUENCE: 253 000 <210> SEQ ID NO 254 <400> SEQUENCE: 254 000 <210> SEQ ID NO 255 <400> SEQUENCE: 255 000 <210> SEQ ID NO 256 <400> SEQUENCE: 256 000 <210> SEQ ID NO 257 <400> SEQUENCE: 257 000 <210> SEQ ID NO 258 <400> SEQUENCE: 258 000 <210> SEQ ID NO 259 <400> SEQUENCE: 259 000 <210> SEQ ID NO 260 <400> SEQUENCE: 260 000 <210> SEQ ID NO 261 <400> SEQUENCE: 261 000 <210> SEQ ID NO 262 <400> SEQUENCE: 262 000 <210> SEQ ID NO 263 <400> SEQUENCE: 263 000 <210> SEQ ID NO 264 <400> SEQUENCE: 264 000 <210> SEQ ID NO 265 <400> SEQUENCE: 265 000 <210> SEQ ID NO 266 <400> SEQUENCE: 266 000 <210> SEQ ID NO 267 <400> SEQUENCE: 267 000 <210> SEQ ID NO 268 <400> SEQUENCE: 268 000 <210> SEQ ID NO 269 <400> SEQUENCE: 269 000 <210> SEQ ID NO 270 <400> SEQUENCE: 270 000 <210> SEQ ID NO 271 <400> SEQUENCE: 271 000 <210> SEQ ID NO 272 <400> SEQUENCE: 272 000 <210> SEQ ID NO 273 <400> SEQUENCE: 273 000 <210> SEQ ID NO 274 <400> SEQUENCE: 274 000 <210> SEQ ID NO 275 <400> SEQUENCE: 275 000 <210> SEQ ID NO 276 <400> SEQUENCE: 276 000 <210> SEQ ID NO 277 <400> SEQUENCE: 277 000 <210> SEQ ID NO 278 <400> SEQUENCE: 278 000 <210> SEQ ID NO 279 <400> SEQUENCE: 279 000 <210> SEQ ID NO 280 <400> SEQUENCE: 280 000 <210> SEQ ID NO 281 <400> SEQUENCE: 281 000 <210> SEQ ID NO 282 <400> SEQUENCE: 282 000 <210> SEQ ID NO 283 <400> SEQUENCE: 283 000 <210> SEQ ID NO 284 <400> SEQUENCE: 284 000 <210> SEQ ID NO 285 <400> SEQUENCE: 285 000 <210> SEQ ID NO 286 <400> SEQUENCE: 286 000 <210> SEQ ID NO 287 <400> SEQUENCE: 287 000 <210> SEQ ID NO 288 <400> SEQUENCE: 288 000 <210> SEQ ID NO 289 <400> SEQUENCE: 289 000 <210> SEQ ID NO 290 <400> SEQUENCE: 290 000 <210> SEQ ID NO 291 <400> SEQUENCE: 291 000 <210> SEQ ID NO 292 <400> SEQUENCE: 292 000 <210> SEQ ID NO 293 <400> SEQUENCE: 293 000 <210> SEQ ID NO 294 <400> SEQUENCE: 294 000 <210> SEQ ID NO 295 <400> SEQUENCE: 295 000 <210> SEQ ID NO 296 <400> SEQUENCE: 296 000 <210> SEQ ID NO 297 <400> SEQUENCE: 297 000 <210> SEQ ID NO 298 <400> SEQUENCE: 298 000 <210> SEQ ID NO 299 <400> SEQUENCE: 299 000 <210> SEQ ID NO 300 <400> SEQUENCE: 300 000 <210> SEQ ID NO 301 <400> SEQUENCE: 301 000 <210> SEQ ID NO 302 <400> SEQUENCE: 302 000 <210> SEQ ID NO 303 <400> SEQUENCE: 303 000 <210> SEQ ID NO 304 <400> SEQUENCE: 304 000 <210> SEQ ID NO 305 <400> SEQUENCE: 305 000 <210> SEQ ID NO 306 <400> SEQUENCE: 306 000 <210> SEQ ID NO 307 <400> SEQUENCE: 307 000 <210> SEQ ID NO 308 <400> SEQUENCE: 308 000 <210> SEQ ID NO 309 <400> SEQUENCE: 309 000 <210> SEQ ID NO 310 <400> SEQUENCE: 310 000 <210> SEQ ID NO 311 <400> SEQUENCE: 311 000 <210> SEQ ID NO 312 <400> SEQUENCE: 312 000 <210> SEQ ID NO 313 <400> SEQUENCE: 313 000 <210> SEQ ID NO 314 <400> SEQUENCE: 314 000 <210> SEQ ID NO 315 <400> SEQUENCE: 315 000 <210> SEQ ID NO 316 <400> SEQUENCE: 316 000 <210> SEQ ID NO 317 <400> SEQUENCE: 317 000 <210> SEQ ID NO 318 <400> SEQUENCE: 318 000 <210> SEQ ID NO 319 <400> SEQUENCE: 319 000 <210> SEQ ID NO 320 <400> SEQUENCE: 320 000 <210> SEQ ID NO 321 <400> SEQUENCE: 321 000 <210> SEQ ID NO 322 <400> SEQUENCE: 322 000 <210> SEQ ID NO 323 <400> SEQUENCE: 323 000 <210> SEQ ID NO 324 <400> SEQUENCE: 324 000 <210> SEQ ID NO 325 <400> SEQUENCE: 325 000 <210> SEQ ID NO 326 <400> SEQUENCE: 326 000 <210> SEQ ID NO 327 <400> SEQUENCE: 327 000 <210> SEQ ID NO 328 <400> SEQUENCE: 328 000 <210> SEQ ID NO 329 <400> SEQUENCE: 329 000 <210> SEQ ID NO 330 <400> SEQUENCE: 330 000 <210> SEQ ID NO 331 <400> SEQUENCE: 331 000 <210> SEQ ID NO 332 <400> SEQUENCE: 332 000 <210> SEQ ID NO 333 <400> SEQUENCE: 333 000 <210> SEQ ID NO 334 <400> SEQUENCE: 334 000 <210> SEQ ID NO 335 <400> SEQUENCE: 335 000 <210> SEQ ID NO 336 <400> SEQUENCE: 336 000 <210> SEQ ID NO 337 <400> SEQUENCE: 337 000 <210> SEQ ID NO 338 <400> SEQUENCE: 338 000 <210> SEQ ID NO 339 <400> SEQUENCE: 339 000 <210> SEQ ID NO 340 <400> SEQUENCE: 340 000 <210> SEQ ID NO 341 <400> SEQUENCE: 341 000 <210> SEQ ID NO 342 <400> SEQUENCE: 342 000 <210> SEQ ID NO 343 <400> SEQUENCE: 343 000 <210> SEQ ID NO 344 <400> SEQUENCE: 344 000 <210> SEQ ID NO 345 <400> SEQUENCE: 345 000 <210> SEQ ID NO 346 <400> SEQUENCE: 346 000 <210> SEQ ID NO 347 <400> SEQUENCE: 347 000 <210> SEQ ID NO 348 <400> SEQUENCE: 348 000 <210> SEQ ID NO 349 <400> SEQUENCE: 349 000 <210> SEQ ID NO 350 <400> SEQUENCE: 350 000 <210> SEQ ID NO 351 <400> SEQUENCE: 351 000 <210> SEQ ID NO 352 <400> SEQUENCE: 352 000 <210> SEQ ID NO 353 <400> SEQUENCE: 353 000 <210> SEQ ID NO 354 <400> SEQUENCE: 354 000 <210> SEQ ID NO 355 <400> SEQUENCE: 355 000 <210> SEQ ID NO 356 <400> SEQUENCE: 356 000 <210> SEQ ID NO 357 <400> SEQUENCE: 357 000 <210> SEQ ID NO 358 <400> SEQUENCE: 358 000 <210> SEQ ID NO 359 <400> SEQUENCE: 359 000 <210> SEQ ID NO 360 <400> SEQUENCE: 360 000 <210> SEQ ID NO 361 <400> SEQUENCE: 361 000 <210> SEQ ID NO 362 <400> SEQUENCE: 362 000 <210> SEQ ID NO 363 <400> SEQUENCE: 363 000 <210> SEQ ID NO 364 <400> SEQUENCE: 364 000 <210> SEQ ID NO 365 <400> SEQUENCE: 365 000 <210> SEQ ID NO 366 <400> SEQUENCE: 366 000 <210> SEQ ID NO 367 <400> SEQUENCE: 367 000 <210> SEQ ID NO 368 <400> SEQUENCE: 368 000 <210> SEQ ID NO 369 <400> SEQUENCE: 369 000 <210> SEQ ID NO 370 <400> SEQUENCE: 370 000 <210> SEQ ID NO 371 <400> SEQUENCE: 371 000 <210> SEQ ID NO 372 <400> SEQUENCE: 372 000 <210> SEQ ID NO 373 <400> SEQUENCE: 373 000 <210> SEQ ID NO 374 <400> SEQUENCE: 374 000 <210> SEQ ID NO 375 <400> SEQUENCE: 375 000 <210> SEQ ID NO 376 <400> SEQUENCE: 376 000 <210> SEQ ID NO 377 <400> SEQUENCE: 377 000 <210> SEQ ID NO 378 <400> SEQUENCE: 378 000 <210> SEQ ID NO 379 <400> SEQUENCE: 379 000 <210> SEQ ID NO 380 <400> SEQUENCE: 380 000 <210> SEQ ID NO 381 <400> SEQUENCE: 381 000 <210> SEQ ID NO 382 <400> SEQUENCE: 382 000 <210> SEQ ID NO 383 <400> SEQUENCE: 383 000 <210> SEQ ID NO 384 <400> SEQUENCE: 384 000 <210> SEQ ID NO 385 <400> SEQUENCE: 385 000 <210> SEQ ID NO 386 <400> SEQUENCE: 386 000 <210> SEQ ID NO 387 <400> SEQUENCE: 387 000 <210> SEQ ID NO 388 <400> SEQUENCE: 388 000 <210> SEQ ID NO 389 <400> SEQUENCE: 389 000 <210> SEQ ID NO 390 <400> SEQUENCE: 390 000 <210> SEQ ID NO 391 <400> SEQUENCE: 391 000 <210> SEQ ID NO 392 <400> SEQUENCE: 392 000 <210> SEQ ID NO 393 <400> SEQUENCE: 393 000 <210> SEQ ID NO 394 <400> SEQUENCE: 394 000 <210> SEQ ID NO 395 <400> SEQUENCE: 395 000 <210> SEQ ID NO 396 <400> SEQUENCE: 396 000 <210> SEQ ID NO 397 <400> SEQUENCE: 397 000 <210> SEQ ID NO 398 <400> SEQUENCE: 398 000 <210> SEQ ID NO 399 <400> SEQUENCE: 399 000 <210> SEQ ID NO 400 <400> SEQUENCE: 400 000 <210> SEQ ID NO 401 <400> SEQUENCE: 401 000 <210> SEQ ID NO 402 <400> SEQUENCE: 402 000 <210> SEQ ID NO 403 <400> SEQUENCE: 403 000 <210> SEQ ID NO 404 <400> SEQUENCE: 404 000 <210> SEQ ID NO 405 <400> SEQUENCE: 405 000 <210> SEQ ID NO 406 <400> SEQUENCE: 406 000 <210> SEQ ID NO 407 <400> SEQUENCE: 407 000 <210> SEQ ID NO 408 <400> SEQUENCE: 408 000 <210> SEQ ID NO 409 <400> SEQUENCE: 409 000 <210> SEQ ID NO 410 <400> SEQUENCE: 410 000 <210> SEQ ID NO 411 <400> SEQUENCE: 411 000 <210> SEQ ID NO 412 <400> SEQUENCE: 412 000 <210> SEQ ID NO 413 <400> SEQUENCE: 413 000 <210> SEQ ID NO 414 <400> SEQUENCE: 414 000 <210> SEQ ID NO 415 <400> SEQUENCE: 415 000 <210> SEQ ID NO 416 <400> SEQUENCE: 416 000 <210> SEQ ID NO 417 <400> SEQUENCE: 417 000 <210> SEQ ID NO 418 <400> SEQUENCE: 418 000 <210> SEQ ID NO 419 <400> SEQUENCE: 419 000 <210> SEQ ID NO 420 <400> SEQUENCE: 420 000 <210> SEQ ID NO 421 <400> SEQUENCE: 421 000 <210> SEQ ID NO 422 <400> SEQUENCE: 422 000 <210> SEQ ID NO 423 <400> SEQUENCE: 423 000 <210> SEQ ID NO 424 <400> SEQUENCE: 424 000 <210> SEQ ID NO 425 <400> SEQUENCE: 425 000 <210> SEQ ID NO 426 <400> SEQUENCE: 426 000 <210> SEQ ID NO 427 <400> SEQUENCE: 427 000 <210> SEQ ID NO 428 <400> SEQUENCE: 428 000 <210> SEQ ID NO 429 <400> SEQUENCE: 429 000 <210> SEQ ID NO 430 <400> SEQUENCE: 430 000 <210> SEQ ID NO 431 <400> SEQUENCE: 431 000 <210> SEQ ID NO 432 <400> SEQUENCE: 432 000 <210> SEQ ID NO 433 <400> SEQUENCE: 433 000 <210> SEQ ID NO 434 <400> SEQUENCE: 434 000 <210> SEQ ID NO 435 <400> SEQUENCE: 435 000 <210> SEQ ID NO 436 <400> SEQUENCE: 436 000 <210> SEQ ID NO 437 <400> SEQUENCE: 437 000 <210> SEQ ID NO 438 <400> SEQUENCE: 438 000 <210> SEQ ID NO 439 <400> SEQUENCE: 439 000 <210> SEQ ID NO 440 <400> SEQUENCE: 440 000 <210> SEQ ID NO 441 <400> SEQUENCE: 441 000 <210> SEQ ID NO 442 <400> SEQUENCE: 442 000 <210> SEQ ID NO 443 <400> SEQUENCE: 443 000 <210> SEQ ID NO 444 <400> SEQUENCE: 444 000 <210> SEQ ID NO 445 <400> SEQUENCE: 445 000 <210> SEQ ID NO 446 <400> SEQUENCE: 446 000 <210> SEQ ID NO 447 <400> SEQUENCE: 447 000 <210> SEQ ID NO 448 <400> SEQUENCE: 448 000 <210> SEQ ID NO 449 <400> SEQUENCE: 449 000 <210> SEQ ID NO 450 <400> SEQUENCE: 450 000 <210> SEQ ID NO 451 <400> SEQUENCE: 451 000 <210> SEQ ID NO 452 <400> SEQUENCE: 452 000 <210> SEQ ID NO 453 <400> SEQUENCE: 453 000 <210> SEQ ID NO 454 <400> SEQUENCE: 454 000 <210> SEQ ID NO 455 <400> SEQUENCE: 455 000 <210> SEQ ID NO 456 <400> SEQUENCE: 456 000 <210> SEQ ID NO 457 <400> SEQUENCE: 457 000 <210> SEQ ID NO 458 <400> SEQUENCE: 458 000 <210> SEQ ID NO 459 <400> SEQUENCE: 459 000 <210> SEQ ID NO 460 <400> SEQUENCE: 460 000 <210> SEQ ID NO 461 <400> SEQUENCE: 461 000 <210> SEQ ID NO 462 <400> SEQUENCE: 462 000 <210> SEQ ID NO 463 <400> SEQUENCE: 463 000 <210> SEQ ID NO 464 <400> SEQUENCE: 464 000 <210> SEQ ID NO 465 <400> SEQUENCE: 465 000 <210> SEQ ID NO 466 <400> SEQUENCE: 466 000 <210> SEQ ID NO 467 <400> SEQUENCE: 467 000 <210> SEQ ID NO 468 <400> SEQUENCE: 468 000 <210> SEQ ID NO 469 <400> SEQUENCE: 469 000 <210> SEQ ID NO 470 <400> SEQUENCE: 470 000 <210> SEQ ID NO 471 <400> SEQUENCE: 471 000 <210> SEQ ID NO 472 <400> SEQUENCE: 472 000 <210> SEQ ID NO 473 <400> SEQUENCE: 473 000 <210> SEQ ID NO 474 <400> SEQUENCE: 474 000 <210> SEQ ID NO 475 <400> SEQUENCE: 475 000 <210> SEQ ID NO 476 <400> SEQUENCE: 476 000 <210> SEQ ID NO 477 <400> SEQUENCE: 477 000 <210> SEQ ID NO 478 <400> SEQUENCE: 478 000 <210> SEQ ID NO 479 <400> SEQUENCE: 479 000 <210> SEQ ID NO 480 <400> SEQUENCE: 480 000 <210> SEQ ID NO 481 <400> SEQUENCE: 481 000 <210> SEQ ID NO 482 <400> SEQUENCE: 482 000 <210> SEQ ID NO 483 <400> SEQUENCE: 483 000 <210> SEQ ID NO 484 <400> SEQUENCE: 484 000 <210> SEQ ID NO 485 <400> SEQUENCE: 485 000 <210> SEQ ID NO 486 <400> SEQUENCE: 486 000 <210> SEQ ID NO 487 <400> SEQUENCE: 487 000 <210> SEQ ID NO 488 <400> SEQUENCE: 488 000 <210> SEQ ID NO 489 <400> SEQUENCE: 489 000 <210> SEQ ID NO 490 <400> SEQUENCE: 490 000 <210> SEQ ID NO 491 <400> SEQUENCE: 491 000 <210> SEQ ID NO 492 <400> SEQUENCE: 492 000 <210> SEQ ID NO 493 <400> SEQUENCE: 493 000 <210> SEQ ID NO 494 <400> SEQUENCE: 494 000 <210> SEQ ID NO 495 <400> SEQUENCE: 495 000 <210> SEQ ID NO 496 <400> SEQUENCE: 496 000 <210> SEQ ID NO 497 <400> SEQUENCE: 497 000 <210> SEQ ID NO 498 <400> SEQUENCE: 498 000 <210> SEQ ID NO 499 <400> SEQUENCE: 499 000 <210> SEQ ID NO 500 <400> SEQUENCE: 500 000 <210> SEQ ID NO 501 <400> SEQUENCE: 501 000 <210> SEQ ID NO 502 <400> SEQUENCE: 502 000 <210> SEQ ID NO 503 <400> SEQUENCE: 503 000 <210> SEQ ID NO 504 <400> SEQUENCE: 504 000 <210> SEQ ID NO 505 <400> SEQUENCE: 505 000 <210> SEQ ID NO 506 <400> SEQUENCE: 506 000 <210> SEQ ID NO 507 <400> SEQUENCE: 507 000 <210> SEQ ID NO 508 <400> SEQUENCE: 508 000 <210> SEQ ID NO 509 <400> SEQUENCE: 509 000 <210> SEQ ID NO 510 <400> SEQUENCE: 510 000 <210> SEQ ID NO 511 <400> SEQUENCE: 511 000 <210> SEQ ID NO 512 <400> SEQUENCE: 512 000 <210> SEQ ID NO 513 <400> SEQUENCE: 513 000 <210> SEQ ID NO 514 <400> SEQUENCE: 514 000 <210> SEQ ID NO 515 <400> SEQUENCE: 515 000 <210> SEQ ID NO 516 <400> SEQUENCE: 516 000 <210> SEQ ID NO 517 <400> SEQUENCE: 517 000 <210> SEQ ID NO 518 <400> SEQUENCE: 518 000 <210> SEQ ID NO 519 <400> SEQUENCE: 519 000 <210> SEQ ID NO 520 <400> SEQUENCE: 520 000 <210> SEQ ID NO 521 <400> SEQUENCE: 521 000 <210> SEQ ID NO 522 <400> SEQUENCE: 522 000 <210> SEQ ID NO 523 <400> SEQUENCE: 523 000 <210> SEQ ID NO 524 <400> SEQUENCE: 524 000 <210> SEQ ID NO 525 <400> SEQUENCE: 525 000 <210> SEQ ID NO 526 <400> SEQUENCE: 526 000 <210> SEQ ID NO 527 <400> SEQUENCE: 527 000 <210> SEQ ID NO 528 <400> SEQUENCE: 528 000 <210> SEQ ID NO 529 <400> SEQUENCE: 529 000 <210> SEQ ID NO 530 <400> SEQUENCE: 530 000 <210> SEQ ID NO 531 <400> SEQUENCE: 531 000 <210> SEQ ID NO 532 <400> SEQUENCE: 532 000 <210> SEQ ID NO 533 <400> SEQUENCE: 533 000 <210> SEQ ID NO 534 <400> SEQUENCE: 534 000 <210> SEQ ID NO 535 <400> SEQUENCE: 535 000 <210> SEQ ID NO 536 <400> SEQUENCE: 536 000 <210> SEQ ID NO 537 <400> SEQUENCE: 537 000 <210> SEQ ID NO 538 <400> SEQUENCE: 538 000 <210> SEQ ID NO 539 <400> SEQUENCE: 539 000 <210> SEQ ID NO 540 <400> SEQUENCE: 540 000 <210> SEQ ID NO 541 <400> SEQUENCE: 541 000 <210> SEQ ID NO 542 <400> SEQUENCE: 542 000 <210> SEQ ID NO 543 <400> SEQUENCE: 543 000 <210> SEQ ID NO 544 <400> SEQUENCE: 544 000 <210> SEQ ID NO 545 <400> SEQUENCE: 545 000 <210> SEQ ID NO 546 <400> SEQUENCE: 546 000 <210> SEQ ID NO 547 <400> SEQUENCE: 547 000 <210> SEQ ID NO 548 <400> SEQUENCE: 548 000 <210> SEQ ID NO 549 <400> SEQUENCE: 549 000 <210> SEQ ID NO 550 <400> SEQUENCE: 550 000 <210> SEQ ID NO 551 <400> SEQUENCE: 551 000 <210> SEQ ID NO 552 <400> SEQUENCE: 552 000 <210> SEQ ID NO 553 <400> SEQUENCE: 553 000 <210> SEQ ID NO 554 <400> SEQUENCE: 554 000 <210> SEQ ID NO 555 <400> SEQUENCE: 555 000 <210> SEQ ID NO 556 <400> SEQUENCE: 556 000 <210> SEQ ID NO 557 <400> SEQUENCE: 557 000 <210> SEQ ID NO 558 <400> SEQUENCE: 558 000 <210> SEQ ID NO 559 <400> SEQUENCE: 559 000 <210> SEQ ID NO 560 <400> SEQUENCE: 560 000 <210> SEQ ID NO 561 <400> SEQUENCE: 561 000 <210> SEQ ID NO 562 <400> SEQUENCE: 562 000 <210> SEQ ID NO 563 <211> LENGTH: 290 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNR Responsive Promoter <400> SEQUENCE: 563 gtcagcataa caccctgacc tctcattaat tgttcatgcc gggcggcact atcgtcgtcc 60 ggccttttcc tctcttactc tgctacgtac atctatttct ataaatccgt tcaatttgtc 120 tgttttttgc acaaacatga aatatcagac aattccgtga cttaagaaaa tttatacaaa 180 tcagcaatat accccttaag gagtatataa aggtgaattt gatttacatc aataagcggg 240 gttgctgaat cgttaaggta ggcggtaata gaaaagaaat cgaggcaaaa 290 <210> SEQ ID NO 564 <211> LENGTH: 173 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNR Responsive Promoter <400> SEQUENCE: 564 atttcctctc atcccatccg gggtgagagt cttttccccc gacttatggc tcatgcatgc 60 atcaaaaaag atgtgagctt gatcaaaaac aaaaaatatt tcactcgaca ggagtattta 120 tattgcgccc gttacgtggg cttcgactgt aaatcagaaa ggagaaaaca cct 173 <210> SEQ ID NO 565 <211> LENGTH: 305 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNR Responsive Promoter <400> SEQUENCE: 565 gtcagcataa caccctgacc tctcattaat tgttcatgcc gggcggcact atcgtcgtcc 60 ggccttttcc tctcttactc tgctacgtac atctatttct ataaatccgt tcaatttgtc 120 tgttttttgc acaaacatga aatatcagac aattccgtga cttaagaaaa tttatacaaa 180 tcagcaatat accccttaag gagtatataa aggtgaattt gatttacatc aataagcggg 240 gttgctgaat cgttaaggat ccctctagaa ataattttgt ttaactttaa gaaggagata 300 tacat 305 <210> SEQ ID NO 566 <211> LENGTH: 180 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNR Responsive Promoter <400> SEQUENCE: 566 catttcctct catcccatcc ggggtgagag tcttttcccc cgacttatgg ctcatgcatg 60 catcaaaaaa gatgtgagct tgatcaaaaa caaaaaatat ttcactcgac aggagtattt 120 atattgcgcc cggatccctc tagaaataat tttgtttaac tttaagaagg agatatacat 180 <210> SEQ ID NO 567 <211> LENGTH: 199 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNR Responsive Promoter <400> SEQUENCE: 567 agttgttctt attggtggtg ttgctttatg gttgcatcgt agtaaatggt tgtaacaaaa 60 gcaatttttc cggctgtctg tatacaaaaa cgccgtaaag tttgagcgaa gtcaataaac 120 tctctaccca ttcagggcaa tatctctctt ggatccctct agaaataatt ttgtttaact 180 ttaagaagga gatatacat 199 <210> SEQ ID NO 568 <211> LENGTH: 117 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNR-responsive regulatory region <400> SEQUENCE: 568 atccccatca ctcttgatgg agatcaattc cccaagctgc tagagcgtta ccttgccctt 60 aaacattagc aatgtcgatt tatcagaggg ccgacaggct cccacaggag aaaaccg 117 <210> SEQ ID NO 569 <211> LENGTH: 108 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNR-responsive regulatory region <400> SEQUENCE: 569 ctcttgatcg ttatcaattc ccacgctgtt tcagagcgtt accttgccct taaacattag 60 caatgtcgat ttatcagagg gccgacaggc tcccacagga gaaaaccg 108 <210> SEQ ID NO 570 <211> LENGTH: 290 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: nirB1 , FNR-responsive regulatory region <400> SEQUENCE: 570 gtcagcataa caccctgacc tctcattaat tgttcatgcc gggcggcact atcgtcgtcc 60 ggccttttcc tctcttactc tgctacgtac atctatttct ataaatccgt tcaatttgtc 120 tgttttttgc acaaacatga aatatcagac aattccgtga cttaagaaaa tttatacaaa 180 tcagcaatat accccttaag gagtatataa aggtgaattt gatttacatc aataagcggg 240 gttgctgaat cgttaaggta ggcggtaata gaaaagaaat cgaggcaaaa 290 <210> SEQ ID NO 571 <211> LENGTH: 433 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: nirB2 , FNR-responsive regulatory region <400> SEQUENCE: 571 cggcccgatc gttgaacata gcggtccgca ggcggcactg cttacagcaa acggtctgta 60 cgctgtcgtc tttgtgatgt gcttcctgtt aggtttcgtc agccgtcacc gtcagcataa 120 caccctgacc tctcattaat tgctcatgcc ggacggcact atcgtcgtcc ggccttttcc 180 tctcttcccc cgctacgtgc atctatttct ataaacccgc tcattttgtc tattttttgc 240 acaaacatga aatatcagac aattccgtga cttaagaaaa tttatacaaa tcagcaatat 300 acccattaag gagtatataa aggtgaattt gatttacatc aataagcggg gttgctgaat 360 cgttaaggta ggcggtaata gaaaagaaat cgaggcaaaa atgtttgttt aactttaaga 420 aggagatata cat 433 <210> SEQ ID NO 572 <211> LENGTH: 290 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: nirB3 , FNR-responsive regulatory region <400> SEQUENCE: 572 gtcagcataa caccctgacc tctcattaat tgctcatgcc ggacggcact atcgtcgtcc 60 ggccttttcc tctcttcccc cgctacgtgc atctatttct ataaacccgc tcattttgtc 120 tattttttgc acaaacatga aatatcagac aattccgtga cttaagaaaa tttatacaaa 180 tcagcaatat acccattaag gagtatataa aggtgaattt gatttacatc aataagcggg 240 gttgctgaat cgttaaggta ggcggtaata gaaaagaaat cgaggcaaaa 290 <210> SEQ ID NO 573 <211> LENGTH: 173 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: ydfZ , FNR-responsive regulatory region <400> SEQUENCE: 573 atttcctctc atcccatccg gggtgagagt cttttccccc gacttatggc tcatgcatgc 60 atcaaaaaag atgtgagctt gatcaaaaac aaaaaatatt tcactcgaca ggagtattta 120 tattgcgccc gttacgtggg cttcgactgt aaatcagaaa ggagaaaaca cct 173 <210> SEQ ID NO 574 <211> LENGTH: 305 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: nirB+RBS , FNR-responsive regulatory region <400> SEQUENCE: 574 gtcagcataa caccctgacc tctcattaat tgttcatgcc gggcggcact atcgtcgtcc 60 ggccttttcc tctcttactc tgctacgtac atctatttct ataaatccgt tcaatttgtc 120 tgttttttgc acaaacatga aatatcagac aattccgtga cttaagaaaa tttatacaaa 180 tcagcaatat accccttaag gagtatataa aggtgaattt gatttacatc aataagcggg 240 gttgctgaat cgttaaggat ccctctagaa ataattttgt ttaactttaa gaaggagata 300 tacat 305 <210> SEQ ID NO 575 <211> LENGTH: 180 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: ydfZ+RBS , FNR-responsive regulatory region <400> SEQUENCE: 575 catttcctct catcccatcc ggggtgagag tcttttcccc cgacttatgg ctcatgcatg 60 catcaaaaaa gatgtgagct tgatcaaaaa caaaaaatat ttcactcgac aggagtattt 120 atattgcgcc cggatccctc tagaaataat tttgtttaac tttaagaagg agatatacat 180 <210> SEQ ID NO 576 <211> LENGTH: 199 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNRS1 , FNR-responsive regulatory region <400> SEQUENCE: 576 agttgttctt attggtggtg ttgctttatg gttgcatcgt agtaaatggt tgtaacaaaa 60 gcaatttttc cggctgtctg tatacaaaaa cgccgtaaag tttgagcgaa gtcaataaac 120 tctctaccca ttcagggcaa tatctctctt ggatccctct agaaataatt ttgtttaact 180 ttaagaagga gatatacat 199 <210> SEQ ID NO 577 <211> LENGTH: 207 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNRS2 , FNR-responsive regulatory region <400> SEQUENCE: 577 agttgttctt attggtggtg ttgctttatg gttgcatcgt agtaaatggt tgtaacaaaa 60 gcaatttttc cggctgtctg tatacaaaaa cgccgcaaag tttgagcgaa gtcaataaac 120 tctctaccca ttcagggcaa tatctctctt ggatccaaag tgaactctag aaataatttt 180 gtttaacttt aagaaggaga tatacat 207 <210> SEQ ID NO 578 <211> LENGTH: 390 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: nirB+crp , FNR-responsive regulatory region <400> SEQUENCE: 578 tcgtctttgt gatgtgcttc ctgttaggtt tcgtcagccg tcaccgtcag cataacaccc 60 tgacctctca ttaattgctc atgccggacg gcactatcgt cgtccggcct tttcctctct 120 tcccccgcta cgtgcatcta tttctataaa cccgctcatt ttgtctattt tttgcacaaa 180 catgaaatat cagacaattc cgtgacttaa gaaaatttat acaaatcagc aatataccca 240 ttaaggagta tataaaggtg aatttgattt acatcaataa gcggggttgc tgaatcgtta 300 aggtagaaat gtgatctagt tcacatttgc ggtaatagaa aagaaatcga ggcaaaaatg 360 tttgtttaac tttaagaagg agatatacat 390 <210> SEQ ID NO 579 <211> LENGTH: 200 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNRS+crp , FNR-responsive regulatory region <400> SEQUENCE: 579 agttgttctt attggtggtg ttgctttatg gttgcatcgt agtaaatggt tgtaacaaaa 60 gcaatttttc cggctgtctg tatacaaaaa cgccgcaaag tttgagcgaa gtcaataaac 120 tctctaccca ttcagggcaa tatctctcaa atgtgatcta gttcacattt tttgtttaac 180 tttaagaagg agatatacat 200 <210> SEQ ID NO 580 <400> SEQUENCE: 580 000 <210> SEQ ID NO 581 <400> SEQUENCE: 581 000 <210> SEQ ID NO 582 <400> SEQUENCE: 582 000 <210> SEQ ID NO 583 <400> SEQUENCE: 583 000 <210> SEQ ID NO 584 <400> SEQUENCE: 584 000 <210> SEQ ID NO 585 <400> SEQUENCE: 585 000 <210> SEQ ID NO 586 <400> SEQUENCE: 586 000 <210> SEQ ID NO 587 <400> SEQUENCE: 587 000 <210> SEQ ID NO 588 <400> SEQUENCE: 588 000 <210> SEQ ID NO 589 <400> SEQUENCE: 589 000 <210> SEQ ID NO 590 <400> SEQUENCE: 590 000 <210> SEQ ID NO 591 <400> SEQUENCE: 591 000 <210> SEQ ID NO 592 <400> SEQUENCE: 592 000 <210> SEQ ID NO 593 <400> SEQUENCE: 593 000 <210> SEQ ID NO 594 <400> SEQUENCE: 594 000 <210> SEQ ID NO 595 <400> SEQUENCE: 595 000 <210> SEQ ID NO 596 <400> SEQUENCE: 596 000 <210> SEQ ID NO 597 <400> SEQUENCE: 597 000 <210> SEQ ID NO 598 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I14018 <400> SEQUENCE: 598 gtttatacat aggcgagtac tctgttatgg 30 <210> SEQ ID NO 599 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I14033 <400> SEQUENCE: 599 agaggttcca actttcacca taatgaaaca 30 <210> SEQ ID NO 600 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I14034 <400> SEQUENCE: 600 taaacaacta acggacaatt ctacctaaca 30 <210> SEQ ID NO 601 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I732021 <400> SEQUENCE: 601 acatcaagcc aaattaaaca ggattaacac 30 <210> SEQ ID NO 602 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I742126 <400> SEQUENCE: 602 gaggtaaaat agtcaacacg cacggtgtta 30 <210> SEQ ID NO 603 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J01006 <400> SEQUENCE: 603 caggccggaa taactcccta taatgcgcca 30 <210> SEQ ID NO 604 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23100 <400> SEQUENCE: 604 ggctagctca gtcctaggta cagtgctagc 30 <210> SEQ ID NO 605 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23101 <400> SEQUENCE: 605 agctagctca gtcctaggta ttatgctagc 30 <210> SEQ ID NO 606 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23102 <400> SEQUENCE: 606 agctagctca gtcctaggta ctgtgctagc 30 <210> SEQ ID NO 607 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23103 <400> SEQUENCE: 607 agctagctca gtcctaggga ttatgctagc 30 <210> SEQ ID NO 608 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23104 <400> SEQUENCE: 608 agctagctca gtcctaggta ttgtgctagc 30 <210> SEQ ID NO 609 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23105 <400> SEQUENCE: 609 ggctagctca gtcctaggta ctatgctagc 30 <210> SEQ ID NO 610 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23106 <400> SEQUENCE: 610 ggctagctca gtcctaggta tagtgctagc 30 <210> SEQ ID NO 611 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23107 <400> SEQUENCE: 611 ggctagctca gccctaggta ttatgctagc 30 <210> SEQ ID NO 612 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23108 <400> SEQUENCE: 612 agctagctca gtcctaggta taatgctagc 30 <210> SEQ ID NO 613 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23109 <400> SEQUENCE: 613 agctagctca gtcctaggga ctgtgctagc 30 <210> SEQ ID NO 614 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23110 <400> SEQUENCE: 614 ggctagctca gtcctaggta caatgctagc 30 <210> SEQ ID NO 615 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23111 <400> SEQUENCE: 615 ggctagctca gtcctaggta tagtgctagc 30 <210> SEQ ID NO 616 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23112 <400> SEQUENCE: 616 agctagctca gtcctaggga ttatgctagc 30 <210> SEQ ID NO 617 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23113 <400> SEQUENCE: 617 ggctagctca gtcctaggga ttatgctagc 30 <210> SEQ ID NO 618 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23114 <400> SEQUENCE: 618 ggctagctca gtcctaggta caatgctagc 30 <210> SEQ ID NO 619 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23115 <400> SEQUENCE: 619 agctagctca gcccttggta caatgctagc 30 <210> SEQ ID NO 620 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23116 <400> SEQUENCE: 620 agctagctca gtcctaggga ctatgctagc 30 <210> SEQ ID NO 621 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23117 <400> SEQUENCE: 621 agctagctca gtcctaggga ttgtgctagc 30 <210> SEQ ID NO 622 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23118 <400> SEQUENCE: 622 ggctagctca gtcctaggta ttgtgctagc 30 <210> SEQ ID NO 623 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23119 <400> SEQUENCE: 623 agctagctca gtcctaggta taatgctagc 30 <210> SEQ ID NO 624 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23150 <400> SEQUENCE: 624 ggctagctca gtcctaggta ttatgctagc 30 <210> SEQ ID NO 625 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23151 <400> SEQUENCE: 625 ggctagctca gtcctaggta caatgctagc 30 <210> SEQ ID NO 626 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J44002 <400> SEQUENCE: 626 aaagtgtgac gccgtgcaaa taatcaatgt 30 <210> SEQ ID NO 627 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J48104 <400> SEQUENCE: 627 gacgaatact taaaatcgtc atacttattt 30 <210> SEQ ID NO 628 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J54200 <400> SEQUENCE: 628 aaacctttcg cggtatggca tgatagcgcc 30 <210> SEQ ID NO 629 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J56015 <400> SEQUENCE: 629 tgatagcgcc cggaagagag tcaattcagg 30 <210> SEQ ID NO 630 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J64951 <400> SEQUENCE: 630 ttatttaccg tgacgaacta attgctcgtg 30 <210> SEQ ID NO 631 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K088007 <400> SEQUENCE: 631 catacgccgt tatacgttgt ttacgctttg 30 <210> SEQ ID NO 632 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K119000 <400> SEQUENCE: 632 ttatgcttcc ggctcgtatg ttgtgtggac 30 <210> SEQ ID NO 633 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K119001 <400> SEQUENCE: 633 ttatgcttcc ggctcgtatg gtgtgtggac 30 <210> SEQ ID NO 634 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1330002 <400> SEQUENCE: 634 ggctagctca gtcctaggta ctatgctagc 30 <210> SEQ ID NO 635 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137029 <400> SEQUENCE: 635 atatatatat atatataatg gaagcgtttt 30 <210> SEQ ID NO 636 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137030 <400> SEQUENCE: 636 atatatatat atatataatg gaagcgtttt 30 <210> SEQ ID NO 637 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137031 <400> SEQUENCE: 637 ccccgaaagc ttaagaatat aattgtaagc 30 <210> SEQ ID NO 638 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137032 <400> SEQUENCE: 638 ccccgaaagc ttaagaatat aattgtaagc 30 <210> SEQ ID NO 639 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137085 <400> SEQUENCE: 639 tgacaatata tatatatata taatgctagc 30 <210> SEQ ID NO 640 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137086 <400> SEQUENCE: 640 acaatatata tatatatata taatgctagc 30 <210> SEQ ID NO 641 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137087 <400> SEQUENCE: 641 aatatatata tatatatata taatgctagc 30 <210> SEQ ID NO 642 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137088 <400> SEQUENCE: 642 tatatatata tatatatata taatgctagc 30 <210> SEQ ID NO 643 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137089 <400> SEQUENCE: 643 tatatatata tatatatata taatgctagc 30 <210> SEQ ID NO 644 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137090 <400> SEQUENCE: 644 aaaaaaaaaa aaaaaaaata taatgctagc 30 <210> SEQ ID NO 645 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137091 <400> SEQUENCE: 645 aaaaaaaaaa aaaaaaaata taatgctagc 30 <210> SEQ ID NO 646 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585100 <400> SEQUENCE: 646 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 647 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585101 <400> SEQUENCE: 647 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 648 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585102 <400> SEQUENCE: 648 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 649 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585103 <400> SEQUENCE: 649 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 650 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585104 <400> SEQUENCE: 650 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 651 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585105 <400> SEQUENCE: 651 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 652 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585106 <400> SEQUENCE: 652 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 653 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585110 <400> SEQUENCE: 653 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 654 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585113 <400> SEQUENCE: 654 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 655 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585115 <400> SEQUENCE: 655 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 656 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585116 <400> SEQUENCE: 656 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 657 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585117 <400> SEQUENCE: 657 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 658 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585118 <400> SEQUENCE: 658 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 659 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585119 <400> SEQUENCE: 659 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 660 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1824896 <400> SEQUENCE: 660 gattaaagag gagaaatact agagtactag 30 <210> SEQ ID NO 661 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K256002 <400> SEQUENCE: 661 caccttcggg tgggcctttc tgcgtttata 30 <210> SEQ ID NO 662 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K256018 <400> SEQUENCE: 662 caccttcggg tgggcctttc tgcgtttata 30 <210> SEQ ID NO 663 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K256020 <400> SEQUENCE: 663 caccttcggg tgggcctttc tgcgtttata 30 <210> SEQ ID NO 664 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K256033 <400> SEQUENCE: 664 caccttcggg tgggcctttc tgcgtttata 30 <210> SEQ ID NO 665 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K292000 <400> SEQUENCE: 665 ggctagctca gtcctaggta cagtgctagc 30 <210> SEQ ID NO 666 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K292001 <400> SEQUENCE: 666 tgctagctac tagagattaa agaggagaaa 30 <210> SEQ ID NO 667 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K418000 <400> SEQUENCE: 667 ttgtgagcgg ataacaagat actgagcaca 30 <210> SEQ ID NO 668 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K418002 <400> SEQUENCE: 668 ttgtgagcgg ataacaagat actgagcaca 30 <210> SEQ ID NO 669 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K418003 <400> SEQUENCE: 669 ttgtgagcgg ataacaagat actgagcaca 30 <210> SEQ ID NO 670 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823004 <400> SEQUENCE: 670 ggctagctca gtcctaggta cagtgctagc 30 <210> SEQ ID NO 671 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823005 <400> SEQUENCE: 671 agctagctca gtcctaggta ttatgctagc 30 <210> SEQ ID NO 672 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823006 <400> SEQUENCE: 672 agctagctca gtcctaggta ctgtgctagc 30 <210> SEQ ID NO 673 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823007 <400> SEQUENCE: 673 agctagctca gtcctaggga ttatgctagc 30 <210> SEQ ID NO 674 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823008 <400> SEQUENCE: 674 ggctagctca gtcctaggta tagtgctagc 30 <210> SEQ ID NO 675 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823010 <400> SEQUENCE: 675 ggctagctca gtcctaggga ttatgctagc 30 <210> SEQ ID NO 676 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823011 <400> SEQUENCE: 676 ggctagctca gtcctaggta caatgctagc 30 <210> SEQ ID NO 677 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823013 <400> SEQUENCE: 677 agctagctca gtcctaggga ttgtgctagc 30 <210> SEQ ID NO 678 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823014 <400> SEQUENCE: 678 ggctagctca gtcctaggta ttgtgctagc 30 <210> SEQ ID NO 679 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13101 <400> SEQUENCE: 679 cctgttttta tgttattctc tctgtaaagg 30 <210> SEQ ID NO 680 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13102 <400> SEQUENCE: 680 aaatatttgc ttatacaatc ttcctgtttt 30 <210> SEQ ID NO 681 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13103 <400> SEQUENCE: 681 gctgataaac cgatacaatt aaaggctcct 30 <210> SEQ ID NO 682 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13104 <400> SEQUENCE: 682 ctcttctcag cgtcttaatc taagctatcg 30 <210> SEQ ID NO 683 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13105 <400> SEQUENCE: 683 atgagccagt tcttaaaatc gcataaggta 30 <210> SEQ ID NO 684 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13106 <400> SEQUENCE: 684 ctattgattg tgacaaaata aacttattcc 30 <210> SEQ ID NO 685 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13108 <400> SEQUENCE: 685 gtttcgcgct tggtataatc gctgggggtc 30 <210> SEQ ID NO 686 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13110 <400> SEQUENCE: 686 ctttgcttct gactataata gtcagggtaa 30 <210> SEQ ID NO 687 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M31519 <400> SEQUENCE: 687 aaaccgatac aattaaaggc tcctgctagc 30 <210> SEQ ID NO 688 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_R1074 <400> SEQUENCE: 688 caccacactg atagtgctag tgtagatcac 30 <210> SEQ ID NO 689 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_R1075 <400> SEQUENCE: 689 gccggaataa ctccctataa tgcgccacca 30 <210> SEQ ID NO 690 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_S03331 <400> SEQUENCE: 690 ttgacaagct tttcctcagc tccgtaaact 30 <210> SEQ ID NO 691 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J45992 <400> SEQUENCE: 691 ggtttcaaaa ttgtgatcta tatttaacaa 30 <210> SEQ ID NO 692 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J45993 <400> SEQUENCE: 692 ggtttcaaaa ttgtgatcta tatttaacaa 30 <210> SEQ ID NO 693 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J45504 <400> SEQUENCE: 693 tctattccaa taaagaaatc ttcctgcgtg 30 <210> SEQ ID NO 694 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1895002 <400> SEQUENCE: 694 gaccgaatat atagtggaaa cgtttagatg 30 <210> SEQ ID NO 695 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1895003 <400> SEQUENCE: 695 ccacatcctg tttttaacct taaaatggca 30 <210> SEQ ID NO 696 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K143012 <400> SEQUENCE: 696 aaaaatgggc tcgtgttgta caataaatgt 30 <210> SEQ ID NO 697 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K143013 <400> SEQUENCE: 697 aaaaaaagcg cgcgattatg taaaatataa 30 <210> SEQ ID NO 698 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K780003 <400> SEQUENCE: 698 aattgcagta ggcatgacaa aatggactca 30 <210> SEQ ID NO 699 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823000 <400> SEQUENCE: 699 caagcttttc ctttataata gaatgaatga 30 <210> SEQ ID NO 700 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823002 <400> SEQUENCE: 700 tctaagctag tgtattttgc gtttaatagt 30 <210> SEQ ID NO 701 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823003 <400> SEQUENCE: 701 aatgggctcg tgttgtacaa taaatgtagt 30 <210> SEQ ID NO 702 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K143010 <400> SEQUENCE: 702 atccttatcg ttatgggtat tgtttgtaat 30 <210> SEQ ID NO 703 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K143011 <400> SEQUENCE: 703 taaaagaatt gtgagcggga atacaacaac 30 <210> SEQ ID NO 704 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K143013 <400> SEQUENCE: 704 aaaaaaagcg cgcgattatg taaaatataa 30 <210> SEQ ID NO 705 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K112706 <400> SEQUENCE: 705 tacaaaataa ttcccctgca aacattatca 30 <210> SEQ ID NO 706 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K112707 <400> SEQUENCE: 706 tacaaaataa ttcccctgca aacattatcg 30 <210> SEQ ID NO 707 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I712074 <400> SEQUENCE: 707 agggaataca agctacttgt tctttttgca 30 <210> SEQ ID NO 708 <211> LENGTH: 23 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I719005 <400> SEQUENCE: 708 taatacgact cactataggg aga 23 <210> SEQ ID NO 709 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J34814 <400> SEQUENCE: 709 gaatttaata cgactcacta tagggaga 28 <210> SEQ ID NO 710 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J64997 <400> SEQUENCE: 710 taatacgact cactatagg 19 <210> SEQ ID NO 711 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K113010 <400> SEQUENCE: 711 gagtcgtatt aatacgactc actatagggg 30 <210> SEQ ID NO 712 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K113011 <400> SEQUENCE: 712 agtgagtcgt actacgactc actatagggg 30 <210> SEQ ID NO 713 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K113012 <400> SEQUENCE: 713 gagtcgtatt aatacgactc tctatagggg 30 <210> SEQ ID NO 714 <211> LENGTH: 18 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1614000 <400> SEQUENCE: 714 taatacgact cactatag 18 <210> SEQ ID NO 715 <211> LENGTH: 23 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_R0085 <400> SEQUENCE: 715 taatacgact cactataggg aga 23 <210> SEQ ID NO 716 <211> LENGTH: 23 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_R0180 <400> SEQUENCE: 716 ttatacgact cactataggg aga 23 <210> SEQ ID NO 717 <211> LENGTH: 23 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_R0181 <400> SEQUENCE: 717 gaatacgact cactataggg aga 23 <210> SEQ ID NO 718 <211> LENGTH: 23 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_R0182 <400> SEQUENCE: 718 taatacgtct cactataggg aga 23 <210> SEQ ID NO 719 <211> LENGTH: 23 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_R0183 <400> SEQUENCE: 719 tcatacgact cactataggg aga 23 <210> SEQ ID NO 720 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_Z0251 <400> SEQUENCE: 720 taatacgact cactataggg agaccacaac 30 <210> SEQ ID NO 721 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_Z0252 <400> SEQUENCE: 721 taattgaact cactaaaggg agaccacagc 30 <210> SEQ ID NO 722 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_Z0253 <400> SEQUENCE: 722 cgaagtaata cgactcacta ttagggaaga 30 <210> SEQ ID NO 723 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 723 atttaggtga cactataga 19 <210> SEQ ID NO 724 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I766555 <400> SEQUENCE: 724 acaaacacaa atacacacac taaattaata 30 <210> SEQ ID NO 725 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I766556 <400> SEQUENCE: 725 ccaagcatac aatcaactat ctcatataca 30 <210> SEQ ID NO 726 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I766557 <400> SEQUENCE: 726 gatacaggat acagcggaaa caacttttaa 30 <210> SEQ ID NO 727 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J63005 <400> SEQUENCE: 727 tttcaagcta taccaagcat acaatcaact 30 <210> SEQ ID NO 728 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K105027 <400> SEQUENCE: 728 cctttgcagc ataaattact atacttctat 30 <210> SEQ ID NO 729 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K105028 <400> SEQUENCE: 729 cctttgcagc ataaattact atacttctat 30 <210> SEQ ID NO 730 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K105029 <400> SEQUENCE: 730 cctttgcagc ataaattact atacttctat 30 <210> SEQ ID NO 731 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K105030 <400> SEQUENCE: 731 cctttgcagc ataaattact atacttctat 30 <210> SEQ ID NO 732 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K105031 <400> SEQUENCE: 732 cctttgcagc ataaattact atacttctat 30 <210> SEQ ID NO 733 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K122000 <400> SEQUENCE: 733 ttatctactt tttacaacaa atataaaaca 30 <210> SEQ ID NO 734 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K124000 <400> SEQUENCE: 734 acaaacacaa atacacacac taaattaata 30 <210> SEQ ID NO 735 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K124002 <400> SEQUENCE: 735 gtttcgaata aacacacata aacaaacaaa 30 <210> SEQ ID NO 736 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K319005 <400> SEQUENCE: 736 ccaagcatac aatcaactat ctcatataca 30 <210> SEQ ID NO 737 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M31201 <400> SEQUENCE: 737 accatcaaag gaagctttaa tcttctcata 30 <210> SEQ ID NO 738 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I712004 <400> SEQUENCE: 738 agaacccact gcttactggc ttatcgaaat 30 <210> SEQ ID NO 739 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K076017 <400> SEQUENCE: 739 ggccgttttt ggcttttttg ttagacgaag 30 <210> SEQ ID NO 740 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: Plpp <400> SEQUENCE: 740 ataagtgcct tcccatcaaa aaaatattct caacataaaa aactttgtgt aatacttgta 60 acgcta 66 <210> SEQ ID NO 741 <211> LENGTH: 52 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: PapFAB46 <400> SEQUENCE: 741 aaaaagagta ttgacttcgc atctttttgt acctataata gattcattgc ta 52 <210> SEQ ID NO 742 <211> LENGTH: 59 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: PJ23101+UP element <400> SEQUENCE: 742 ggaaaatttt tttaaaaaaa aaactttaca gctagctcag tcctaggtat tatgctagc 59 <210> SEQ ID NO 743 <211> LENGTH: 59 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: PJ23107+UP element <400> SEQUENCE: 743 ggaaaatttt tttaaaaaaa aaactttacg gctagctcag ccctaggtat tatgctagc 59 <210> SEQ ID NO 744 <211> LENGTH: 64 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: PSYN23119 <400> SEQUENCE: 744 ggaaaatttt tttaaaaaaa aaacttgaca gctagctcag tccttggtat aatgctagca 60 cgaa 64 <210> SEQ ID NO 745 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <220> FEATURE: <223> OTHER INFORMATION: PhoA <400> SEQUENCE: 745 Met Lys Gln Ser Thr Ile Ala Leu Ala Leu Leu Pro Leu Leu Phe Thr 1 5 10 15 Pro Val Thr Lys Ala 20 <210> SEQ ID NO 746 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <220> FEATURE: <223> OTHER INFORMATION: PhoA <400> SEQUENCE: 746 Lys Gln Ser Thr Ile Ala Leu Ala Leu Leu Pro Leu Leu Phe Thr Pro 1 5 10 15 Val Thr Lys Ala 20 <210> SEQ ID NO 747 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <220> FEATURE: <223> OTHER INFORMATION: OmpF <400> SEQUENCE: 747 Met Met Lys Arg Asn Ile Leu Ala Val Ile Val Pro Ala Leu Leu Val 1 5 10 15 Ala Gly Thr Ala Asn Ala 20 <210> SEQ ID NO 748 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <220> FEATURE: <223> OTHER INFORMATION: cvaC <400> SEQUENCE: 748 Met Arg Thr Leu Thr Leu Asn Glu Leu Asp Ser Val Ser Gly Gly 1 5 10 15 <210> SEQ ID NO 749 <211> LENGTH: 43 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <220> FEATURE: <223> OTHER INFORMATION: TorA <400> SEQUENCE: 749 Met Asn Asn Asn Asp Leu Phe Gln Ala Ser Arg Arg Arg Phe Leu Ala 1 5 10 15 Gln Leu Gly Gly Leu Thr Val Ala Gly Met Leu Gly Thr Ser Leu Leu 20 25 30 Thr Pro Arg Arg Ala Thr Ala Ala Gln Ala Ala 35 40 <210> SEQ ID NO 750 <211> LENGTH: 33 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <220> FEATURE: <223> OTHER INFORMATION: fdnG <400> SEQUENCE: 750 Met Asp Val Ser Arg Arg Gln Phe Phe Lys Ile Cys Ala Gly Gly Met 1 5 10 15 Ala Gly Thr Thr Val Ala Ala Leu Gly Phe Ala Pro Lys Gln Ala Leu 20 25 30 Ala <210> SEQ ID NO 751 <211> LENGTH: 45 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <220> FEATURE: <223> OTHER INFORMATION: dmsA <400> SEQUENCE: 751 Met Lys Thr Lys Ile Pro Asp Ala Val Leu Ala Ala Glu Val Ser Arg 1 5 10 15 Arg Gly Leu Val Lys Thr Thr Ala Ile Gly Gly Leu Ala Met Ala Ser 20 25 30 Ser Ala Leu Thr Leu Pro Phe Ser Arg Ile Ala His Ala 35 40 45 <210> SEQ ID NO 752 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <220> FEATURE: <223> OTHER INFORMATION: PelB <400> SEQUENCE: 752 Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala Ala 1 5 10 15 Gln Pro Ala Met Ala 20 <210> SEQ ID NO 753 <211> LENGTH: 52 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <220> FEATURE: <223> OTHER INFORMATION: HlyA secretion signal <400> SEQUENCE: 753 Leu Asn Pro Leu Ile Asn Glu Ile Ser Lys Ile Ile Ser Ala Ala Gly 1 5 10 15 Asn Phe Asp Val Lys Glu Glu Arg Ala Ala Ala Ser Leu Leu Gln Leu 20 25 30 Ser Gly Asn Ala Ser Asp Phe Ser Tyr Gly Arg Asn Ser Ile Thr Leu 35 40 45 Thr Ala Ser Ala 50 <210> SEQ ID NO 754 <211> LENGTH: 159 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: HlyA secretion signal <400> SEQUENCE: 754 cttaatccat taattaatga aatcagcaaa atcatttcag ctgcaggtaa ttttgatgtt 60 aaagaggaaa gagctgcagc ttctttattg cagttgtccg gtaatgccag tgatttttca 120 tatggacgga actcaataac tttgacagca tcagcataa 159 <210> SEQ ID NO 755 <400> SEQUENCE: 755 000 <210> SEQ ID NO 756 <400> SEQUENCE: 756 000 <210> SEQ ID NO 757 <400> SEQUENCE: 757 000 <210> SEQ ID NO 758 <400> SEQUENCE: 758 000 <210> SEQ ID NO 759 <400> SEQUENCE: 759 000 <210> SEQ ID NO 760 <400> SEQUENCE: 760 000 <210> SEQ ID NO 761 <400> SEQUENCE: 761 000 <210> SEQ ID NO 762 <400> SEQUENCE: 762 000 <210> SEQ ID NO 763 <400> SEQUENCE: 763 000 <210> SEQ ID NO 764 <400> SEQUENCE: 764 000 <210> SEQ ID NO 765 <400> SEQUENCE: 765 000 <210> SEQ ID NO 766 <400> SEQUENCE: 766 000 <210> SEQ ID NO 767 <400> SEQUENCE: 767 000 <210> SEQ ID NO 768 <400> SEQUENCE: 768 000 <210> SEQ ID NO 769 <400> SEQUENCE: 769 000 <210> SEQ ID NO 770 <400> SEQUENCE: 770 000 <210> SEQ ID NO 771 <400> SEQUENCE: 771 000 <210> SEQ ID NO 772 <400> SEQUENCE: 772 000 <210> SEQ ID NO 773 <400> SEQUENCE: 773 000 <210> SEQ ID NO 774 <400> SEQUENCE: 774 000 <210> SEQ ID NO 775 <400> SEQUENCE: 775 000 <210> SEQ ID NO 776 <400> SEQUENCE: 776 000 <210> SEQ ID NO 777 <400> SEQUENCE: 777 000 <210> SEQ ID NO 778 <400> SEQUENCE: 778 000 <210> SEQ ID NO 779 <400> SEQUENCE: 779 000 <210> SEQ ID NO 780 <400> SEQUENCE: 780 000 <210> SEQ ID NO 781 <400> SEQUENCE: 781 000 <210> SEQ ID NO 782 <400> SEQUENCE: 782 000 <210> SEQ ID NO 783 <400> SEQUENCE: 783 000 <210> SEQ ID NO 784 <400> SEQUENCE: 784 000 <210> SEQ ID NO 785 <400> SEQUENCE: 785 000 <210> SEQ ID NO 786 <400> SEQUENCE: 786 000 <210> SEQ ID NO 787 <400> SEQUENCE: 787 000 <210> SEQ ID NO 788 <400> SEQUENCE: 788 000 <210> SEQ ID NO 789 <400> SEQUENCE: 789 000 <210> SEQ ID NO 790 <400> SEQUENCE: 790 000 <210> SEQ ID NO 791 <400> SEQUENCE: 791 000 <210> SEQ ID NO 792 <400> SEQUENCE: 792 000 <210> SEQ ID NO 793 <400> SEQUENCE: 793 000 <210> SEQ ID NO 794 <400> SEQUENCE: 794 000 <210> SEQ ID NO 795 <400> SEQUENCE: 795 000 <210> SEQ ID NO 796 <400> SEQUENCE: 796 000 <210> SEQ ID NO 797 <400> SEQUENCE: 797 000 <210> SEQ ID NO 798 <400> SEQUENCE: 798 000 <210> SEQ ID NO 799 <400> SEQUENCE: 799 000 <210> SEQ ID NO 800 <400> SEQUENCE: 800 000 <210> SEQ ID NO 801 <400> SEQUENCE: 801 000 <210> SEQ ID NO 802 <400> SEQUENCE: 802 000 <210> SEQ ID NO 803 <400> SEQUENCE: 803 000 <210> SEQ ID NO 804 <400> SEQUENCE: 804 000 <210> SEQ ID NO 805 <400> SEQUENCE: 805 000 <210> SEQ ID NO 806 <400> SEQUENCE: 806 000 <210> SEQ ID NO 807 <400> SEQUENCE: 807 000 <210> SEQ ID NO 808 <400> SEQUENCE: 808 000 <210> SEQ ID NO 809 <400> SEQUENCE: 809 000 <210> SEQ ID NO 810 <400> SEQUENCE: 810 000 <210> SEQ ID NO 811 <400> SEQUENCE: 811 000 <210> SEQ ID NO 812 <400> SEQUENCE: 812 000 <210> SEQ ID NO 813 <400> SEQUENCE: 813 000 <210> SEQ ID NO 814 <400> SEQUENCE: 814 000 <210> SEQ ID NO 815 <400> SEQUENCE: 815 000 <210> SEQ ID NO 816 <400> SEQUENCE: 816 000 <210> SEQ ID NO 817 <400> SEQUENCE: 817 000 <210> SEQ ID NO 818 <400> SEQUENCE: 818 000 <210> SEQ ID NO 819 <400> SEQUENCE: 819 000 <210> SEQ ID NO 820 <400> SEQUENCE: 820 000 <210> SEQ ID NO 821 <400> SEQUENCE: 821 000 <210> SEQ ID NO 822 <400> SEQUENCE: 822 000 <210> SEQ ID NO 823 <400> SEQUENCE: 823 000 <210> SEQ ID NO 824 <400> SEQUENCE: 824 000 <210> SEQ ID NO 825 <400> SEQUENCE: 825 000 <210> SEQ ID NO 826 <400> SEQUENCE: 826 000 <210> SEQ ID NO 827 <400> SEQUENCE: 827 000 <210> SEQ ID NO 828 <400> SEQUENCE: 828 000 <210> SEQ ID NO 829 <400> SEQUENCE: 829 000 <210> SEQ ID NO 830 <400> SEQUENCE: 830 000 <210> SEQ ID NO 831 <400> SEQUENCE: 831 000 <210> SEQ ID NO 832 <400> SEQUENCE: 832 000 <210> SEQ ID NO 833 <400> SEQUENCE: 833 000 <210> SEQ ID NO 834 <400> SEQUENCE: 834 000 <210> SEQ ID NO 835 <400> SEQUENCE: 835 000 <210> SEQ ID NO 836 <400> SEQUENCE: 836 000 <210> SEQ ID NO 837 <400> SEQUENCE: 837 000 <210> SEQ ID NO 838 <400> SEQUENCE: 838 000 <210> SEQ ID NO 839 <400> SEQUENCE: 839 000 <210> SEQ ID NO 840 <400> SEQUENCE: 840 000 <210> SEQ ID NO 841 <400> SEQUENCE: 841 000 <210> SEQ ID NO 842 <400> SEQUENCE: 842 000 <210> SEQ ID NO 843 <400> SEQUENCE: 843 000 <210> SEQ ID NO 844 <400> SEQUENCE: 844 000 <210> SEQ ID NO 845 <400> SEQUENCE: 845 000 <210> SEQ ID NO 846 <400> SEQUENCE: 846 000 <210> SEQ ID NO 847 <400> SEQUENCE: 847 000 <210> SEQ ID NO 848 <400> SEQUENCE: 848 000 <210> SEQ ID NO 849 <400> SEQUENCE: 849 000 <210> SEQ ID NO 850 <400> SEQUENCE: 850 000 <210> SEQ ID NO 851 <400> SEQUENCE: 851 000 <210> SEQ ID NO 852 <400> SEQUENCE: 852 000 <210> SEQ ID NO 853 <400> SEQUENCE: 853 000 <210> SEQ ID NO 854 <400> SEQUENCE: 854 000 <210> SEQ ID NO 855 <400> SEQUENCE: 855 000 <210> SEQ ID NO 856 <400> SEQUENCE: 856 000 <210> SEQ ID NO 857 <400> SEQUENCE: 857 000 <210> SEQ ID NO 858 <400> SEQUENCE: 858 000 <210> SEQ ID NO 859 <400> SEQUENCE: 859 000 <210> SEQ ID NO 860 <400> SEQUENCE: 860 000 <210> SEQ ID NO 861 <400> SEQUENCE: 861 000 <210> SEQ ID NO 862 <400> SEQUENCE: 862 000 <210> SEQ ID NO 863 <400> SEQUENCE: 863 000 <210> SEQ ID NO 864 <400> SEQUENCE: 864 000 <210> SEQ ID NO 865 <400> SEQUENCE: 865 000 <210> SEQ ID NO 866 <400> SEQUENCE: 866 000 <210> SEQ ID NO 867 <400> SEQUENCE: 867 000 <210> SEQ ID NO 868 <400> SEQUENCE: 868 000 <210> SEQ ID NO 869 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61133 <400> SEQUENCE: 869 tctagagaaa gacccgagac actagatg 28 <210> SEQ ID NO 870 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61134 <400> SEQUENCE: 870 tctagagaaa gaccggaaat actagatg 28 <210> SEQ ID NO 871 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61135 <400> SEQUENCE: 871 tctagagaaa gaccggagac actagatg 28 <210> SEQ ID NO 872 <400> SEQUENCE: 872 000 <210> SEQ ID NO 873 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61132 <400> SEQUENCE: 873 tctagagaaa gacaggatta actagatg 28 <210> SEQ ID NO 874 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61136 <400> SEQUENCE: 874 tctagagaaa gagctgagca actagatg 28 <210> SEQ ID NO 875 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61137 <400> SEQUENCE: 875 tctagagaaa gagtagatca actagatg 28 <210> SEQ ID NO 876 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61138 <400> SEQUENCE: 876 tctagagaaa gatatgaata actagatg 28 <210> SEQ ID NO 877 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61139 <400> SEQUENCE: 877 tctagagaaa gattagagtc actagatg 28 <210> SEQ ID NO 878 <400> SEQUENCE: 878 000 <210> SEQ ID NO 879 <400> SEQUENCE: 879 000 <210> SEQ ID NO 880 <211> LENGTH: 31 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0029 <400> SEQUENCE: 880 tctagagttc acacaggaaa cctactagat g 31 <210> SEQ ID NO 881 <211> LENGTH: 31 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0030 <400> SEQUENCE: 881 tctagagatt aaagaggaga aatactagat g 31 <210> SEQ ID NO 882 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0031 <400> SEQUENCE: 882 tctagagtca cacaggaaac ctactagatg 30 <210> SEQ ID NO 883 <211> LENGTH: 29 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0032 <400> SEQUENCE: 883 tctagagtca cacaggaaag tactagatg 29 <210> SEQ ID NO 884 <211> LENGTH: 27 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0033 <400> SEQUENCE: 884 tctagagtca cacaggacta ctagatg 27 <210> SEQ ID NO 885 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0034 <400> SEQUENCE: 885 tctagagaaa gaggagaaat actagatg 28 <210> SEQ ID NO 886 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0035 <400> SEQUENCE: 886 tctagagatt aaagaggaga atactagatg 30 <210> SEQ ID NO 887 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0064 <400> SEQUENCE: 887 tctagagaaa gaggggaaat actagatg 28 <210> SEQ ID NO 888 <400> SEQUENCE: 888 000 <210> SEQ ID NO 889 <400> SEQUENCE: 889 000 <210> SEQ ID NO 890 <400> SEQUENCE: 890 000 <210> SEQ ID NO 891 <400> SEQUENCE: 891 000 <210> SEQ ID NO 892 <400> SEQUENCE: 892 000 <210> SEQ ID NO 893 <400> SEQUENCE: 893 000 <210> SEQ ID NO 894 <400> SEQUENCE: 894 000 <210> SEQ ID NO 895 <400> SEQUENCE: 895 000 <210> SEQ ID NO 896 <400> SEQUENCE: 896 000 <210> SEQ ID NO 897 <400> SEQUENCE: 897 000 <210> SEQ ID NO 898 <400> SEQUENCE: 898 000 <210> SEQ ID NO 899 <400> SEQUENCE: 899 000 <210> SEQ ID NO 900 <400> SEQUENCE: 900 000 <210> SEQ ID NO 901 <400> SEQUENCE: 901 000 <210> SEQ ID NO 902 <400> SEQUENCE: 902 000 <210> SEQ ID NO 903 <400> SEQUENCE: 903 000 <210> SEQ ID NO 904 <400> SEQUENCE: 904 000 <210> SEQ ID NO 905 <400> SEQUENCE: 905 000 <210> SEQ ID NO 906 <400> SEQUENCE: 906 000 <210> SEQ ID NO 907 <400> SEQUENCE: 907 000 <210> SEQ ID NO 908 <400> SEQUENCE: 908 000 <210> SEQ ID NO 909 <400> SEQUENCE: 909 000 <210> SEQ ID NO 910 <400> SEQUENCE: 910 000 <210> SEQ ID NO 911 <400> SEQUENCE: 911 000 <210> SEQ ID NO 912 <400> SEQUENCE: 912 000 <210> SEQ ID NO 913 <400> SEQUENCE: 913 000 <210> SEQ ID NO 914 <400> SEQUENCE: 914 000 <210> SEQ ID NO 915 <400> SEQUENCE: 915 000 <210> SEQ ID NO 916 <400> SEQUENCE: 916 000 <210> SEQ ID NO 917 <400> SEQUENCE: 917 000 <210> SEQ ID NO 918 <400> SEQUENCE: 918 000 <210> SEQ ID NO 919 <400> SEQUENCE: 919 000 <210> SEQ ID NO 920 <400> SEQUENCE: 920 000 <210> SEQ ID NO 921 <400> SEQUENCE: 921 000 <210> SEQ ID NO 922 <400> SEQUENCE: 922 000 <210> SEQ ID NO 923 <400> SEQUENCE: 923 000 <210> SEQ ID NO 924 <400> SEQUENCE: 924 000 <210> SEQ ID NO 925 <400> SEQUENCE: 925 000 <210> SEQ ID NO 926 <400> SEQUENCE: 926 000 <210> SEQ ID NO 927 <400> SEQUENCE: 927 000 <210> SEQ ID NO 928 <400> SEQUENCE: 928 000 <210> SEQ ID NO 929 <400> SEQUENCE: 929 000 <210> SEQ ID NO 930 <400> SEQUENCE: 930 000 <210> SEQ ID NO 931 <400> SEQUENCE: 931 000 <210> SEQ ID NO 932 <400> SEQUENCE: 932 000 <210> SEQ ID NO 933 <400> SEQUENCE: 933 000 <210> SEQ ID NO 934 <400> SEQUENCE: 934 000 <210> SEQ ID NO 935 <400> SEQUENCE: 935 000 <210> SEQ ID NO 936 <400> SEQUENCE: 936 000 <210> SEQ ID NO 937 <400> SEQUENCE: 937 000 <210> SEQ ID NO 938 <400> SEQUENCE: 938 000 <210> SEQ ID NO 939 <400> SEQUENCE: 939 000 <210> SEQ ID NO 940 <400> SEQUENCE: 940 000 <210> SEQ ID NO 941 <400> SEQUENCE: 941 000 <210> SEQ ID NO 942 <400> SEQUENCE: 942 000 <210> SEQ ID NO 943 <400> SEQUENCE: 943 000 <210> SEQ ID NO 944 <400> SEQUENCE: 944 000 <210> SEQ ID NO 945 <400> SEQUENCE: 945 000 <210> SEQ ID NO 946 <400> SEQUENCE: 946 000 <210> SEQ ID NO 947 <400> SEQUENCE: 947 000 <210> SEQ ID NO 948 <400> SEQUENCE: 948 000 <210> SEQ ID NO 949 <400> SEQUENCE: 949 000 <210> SEQ ID NO 950 <400> SEQUENCE: 950 000 <210> SEQ ID NO 951 <400> SEQUENCE: 951 000 <210> SEQ ID NO 952 <400> SEQUENCE: 952 000 <210> SEQ ID NO 953 <400> SEQUENCE: 953 000 <210> SEQ ID NO 954 <400> SEQUENCE: 954 000 <210> SEQ ID NO 955 <400> SEQUENCE: 955 000 <210> SEQ ID NO 956 <400> SEQUENCE: 956 000 <210> SEQ ID NO 957 <400> SEQUENCE: 957 000 <210> SEQ ID NO 958 <400> SEQUENCE: 958 000 <210> SEQ ID NO 959 <400> SEQUENCE: 959 000 <210> SEQ ID NO 960 <400> SEQUENCE: 960 000 <210> SEQ ID NO 961 <400> SEQUENCE: 961 000 <210> SEQ ID NO 962 <400> SEQUENCE: 962 000 <210> SEQ ID NO 963 <400> SEQUENCE: 963 000 <210> SEQ ID NO 964 <400> SEQUENCE: 964 000 <210> SEQ ID NO 965 <400> SEQUENCE: 965 000 <210> SEQ ID NO 966 <400> SEQUENCE: 966 000 <210> SEQ ID NO 967 <400> SEQUENCE: 967 000 <210> SEQ ID NO 968 <400> SEQUENCE: 968 000 <210> SEQ ID NO 969 <400> SEQUENCE: 969 000 <210> SEQ ID NO 970 <400> SEQUENCE: 970 000 <210> SEQ ID NO 971 <400> SEQUENCE: 971 000 <210> SEQ ID NO 972 <400> SEQUENCE: 972 000 <210> SEQ ID NO 973 <400> SEQUENCE: 973 000 <210> SEQ ID NO 974 <400> SEQUENCE: 974 000 <210> SEQ ID NO 975 <400> SEQUENCE: 975 000 <210> SEQ ID NO 976 <400> SEQUENCE: 976 000 <210> SEQ ID NO 977 <400> SEQUENCE: 977 000 <210> SEQ ID NO 978 <400> SEQUENCE: 978 000 <210> SEQ ID NO 979 <211> LENGTH: 45 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: scFvLinker <400> SEQUENCE: 979 ggtggaggcg gctctggcgg tggtgggagt ggaggcggtg gcagt 45 <210> SEQ ID NO 980 <400> SEQUENCE: 980 000 <210> SEQ ID NO 981 <400> SEQUENCE: 981 000 <210> SEQ ID NO 982 <400> SEQUENCE: 982 000 <210> SEQ ID NO 983 <400> SEQUENCE: 983 000 <210> SEQ ID NO 984 <400> SEQUENCE: 984 000 <210> SEQ ID NO 985 <400> SEQUENCE: 985 000 <210> SEQ ID NO 986 <400> SEQUENCE: 986 000 <210> SEQ ID NO 987 <400> SEQUENCE: 987 000 <210> SEQ ID NO 988 <400> SEQUENCE: 988 000 <210> SEQ ID NO 989 <400> SEQUENCE: 989 000 <210> SEQ ID NO 990 <211> LENGTH: 607 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <220> FEATURE: <223> OTHER INFORMATION: Invasin display tag <400> SEQUENCE: 990 Met Val Phe Gln Pro Ile Ser Glu Phe Leu Leu Ile Arg Asn Ala Gly 1 5 10 15 Met Ser Met Tyr Phe Asn Lys Ile Ile Ser Phe Asn Ile Ile Ser Arg 20 25 30 Ile Val Ile Cys Ile Phe Leu Ile Cys Gly Met Phe Met Ala Gly Ala 35 40 45 Ser Glu Lys Tyr Asp Ala Asn Ala Pro Gln Gln Val Gln Pro Tyr Ser 50 55 60 Val Ser Ser Ser Ala Phe Glu Asn Leu His Pro Asn Asn Glu Met Glu 65 70 75 80 Ser Ser Ile Asn Pro Phe Ser Ala Ser Asp Thr Glu Arg Asn Ala Ala 85 90 95 Ile Ile Asp Arg Ala Asn Lys Glu Gln Glu Thr Glu Ala Val Asn Lys 100 105 110 Met Ile Ser Thr Gly Ala Arg Leu Ala Ala Ser Gly Arg Ala Ser Asp 115 120 125 Val Ala His Ser Met Val Gly Asp Ala Val Asn Gln Glu Ile Lys Gln 130 135 140 Trp Leu Asn Arg Phe Gly Thr Ala Gln Val Asn Leu Asn Phe Asp Lys 145 150 155 160 Asn Phe Ser Leu Lys Glu Ser Ser Leu Asp Trp Leu Ala Pro Trp Tyr 165 170 175 Asp Ser Ala Ser Phe Leu Phe Phe Ser Gln Leu Gly Ile Arg Asn Lys 180 185 190 Asp Ser Arg Asn Thr Leu Asn Leu Gly Val Gly Ile Arg Thr Leu Glu 195 200 205 Asn Gly Trp Leu Tyr Gly Leu Asn Thr Phe Tyr Asp Asn Asp Leu Thr 210 215 220 Gly His Asn His Arg Ile Gly Leu Gly Ala Glu Ala Trp Thr Asp Tyr 225 230 235 240 Leu Gln Leu Ala Ala Asn Gly Tyr Phe Arg Leu Asn Gly Trp His Ser 245 250 255 Ser Arg Asp Phe Ser Asp Tyr Lys Glu Arg Pro Ala Thr Gly Gly Asp 260 265 270 Leu Arg Ala Asn Ala Tyr Leu Pro Ala Leu Pro Gln Leu Gly Gly Lys 275 280 285 Leu Met Tyr Glu Gln Tyr Thr Gly Glu Arg Val Ala Leu Phe Gly Lys 290 295 300 Asp Asn Leu Gln Arg Asn Pro Tyr Ala Val Thr Ala Gly Ile Asn Tyr 305 310 315 320 Thr Pro Val Pro Leu Leu Thr Val Gly Val Asp Gln Arg Met Gly Lys 325 330 335 Ser Ser Lys His Glu Thr Gln Trp Asn Leu Gln Met Asn Tyr Arg Leu 340 345 350 Gly Glu Ser Phe Gln Ser Gln Leu Ser Pro Ser Ala Val Ala Gly Thr 355 360 365 Arg Leu Leu Ala Glu Ser Arg Tyr Asn Leu Val Asp Arg Asn Asn Asn 370 375 380 Ile Val Leu Glu Tyr Gln Lys Gln Gln Val Val Lys Leu Thr Leu Ser 385 390 395 400 Pro Ala Thr Ile Ser Gly Leu Pro Gly Gln Val Tyr Gln Val Asn Ala 405 410 415 Gln Val Gln Gly Ala Ser Ala Val Arg Glu Ile Val Trp Ser Asp Ala 420 425 430 Glu Leu Ile Ala Ala Gly Gly Thr Leu Thr Pro Leu Ser Thr Thr Gln 435 440 445 Phe Asn Leu Val Leu Pro Pro Tyr Lys Arg Thr Ala Gln Val Ser Arg 450 455 460 Val Thr Asp Asp Leu Thr Ala Asn Phe Tyr Ser Leu Ser Ala Leu Ala 465 470 475 480 Val Asp His Gln Gly Asn Arg Ser Asn Ser Phe Thr Leu Ser Val Thr 485 490 495 Val Gln Gln Pro Gln Leu Thr Leu Thr Ala Ala Val Ile Gly Asp Gly 500 505 510 Ala Pro Ala Asn Gly Lys Thr Ala Ile Thr Val Glu Phe Thr Val Ala 515 520 525 Asp Phe Glu Gly Lys Pro Leu Ala Gly Gln Glu Val Val Ile Thr Thr 530 535 540 Asn Asn Gly Ala Leu Pro Asn Lys Ile Thr Glu Lys Thr Asp Ala Asn 545 550 555 560 Gly Val Ala Arg Ile Ala Leu Thr Asn Thr Thr Asp Gly Val Thr Val 565 570 575 Val Thr Ala Glu Val Glu Gly Gln Arg Gln Ser Val Asp Thr His Phe 580 585 590 Val Lys Gly Thr Ile Ala Ala Asp Lys Ser Thr Leu Ala Ala Val 595 600 605 <210> SEQ ID NO 991 <211> LENGTH: 148 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <220> FEATURE: <223> OTHER INFORMATION: LppOmpA display tag <400> SEQUENCE: 991 Lys Ala Thr Lys Leu Val Leu Gly Ala Val Ile Leu Gly Ser Thr Leu 1 5 10 15 Leu Ala Gly Cys Ser Ser Asn Ala Lys Ile Asp Gln Gly Ile Asn Pro 20 25 30 Tyr Val Gly Phe Glu Met Gly Tyr Asp Trp Leu Gly Arg Met Pro Tyr 35 40 45 Lys Gly Ser Val Glu Asn Gly Ala Tyr Lys Ala Gln Gly Val Gln Leu 50 55 60 Thr Ala Lys Leu Gly Tyr Pro Ile Thr Asp Asp Leu Asp Ile Tyr Thr 65 70 75 80 Arg Leu Gly Gly Met Val Trp Arg Ala Asp Thr Lys Ser Asn Val Tyr 85 90 95 Gly Lys Asn His Asp Thr Gly Val Ser Pro Val Phe Ala Gly Gly Val 100 105 110 Glu Tyr Ala Ile Thr Pro Glu Ile Ala Thr Arg Leu Glu Tyr Gln Trp 115 120 125 Thr Asn Asn Ile Gly Asp Ala His Thr Ile Gly Thr Arg Pro Asp Asn 130 135 140 Gly Ile Pro Gly 145 <210> SEQ ID NO 992 <211> LENGTH: 658 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <220> FEATURE: <223> OTHER INFORMATION: IntiminN display tag <400> SEQUENCE: 992 Ile Thr His Gly Cys Tyr Thr Arg Thr Arg His Lys His Lys Leu Lys 1 5 10 15 Lys Thr Leu Ile Met Leu Ser Ala Gly Leu Gly Leu Phe Phe Tyr Val 20 25 30 Asn Gln Asn Ser Phe Ala Asn Gly Glu Asn Tyr Phe Lys Leu Gly Ser 35 40 45 Asp Ser Lys Leu Leu Thr His Asp Ser Tyr Gln Asn Arg Leu Phe Tyr 50 55 60 Thr Leu Lys Thr Gly Glu Thr Val Ala Asp Leu Ser Lys Ser Gln Asp 65 70 75 80 Ile Asn Leu Ser Thr Ile Trp Ser Leu Asn Lys His Leu Tyr Ser Ser 85 90 95 Glu Ser Glu Met Met Lys Ala Ala Pro Gly Gln Gln Ile Ile Leu Pro 100 105 110 Leu Lys Lys Leu Pro Phe Glu Tyr Ser Ala Leu Pro Leu Leu Gly Ser 115 120 125 Ala Pro Leu Val Ala Ala Gly Gly Val Ala Gly His Thr Asn Lys Leu 130 135 140 Thr Lys Met Ser Pro Asp Val Thr Lys Ser Asn Met Thr Asp Asp Lys 145 150 155 160 Ala Leu Asn Tyr Ala Ala Gln Gln Ala Ala Ser Leu Gly Ser Gln Leu 165 170 175 Gln Ser Arg Ser Leu Asn Gly Asp Tyr Ala Lys Asp Thr Ala Leu Gly 180 185 190 Ile Ala Gly Asn Gln Ala Ser Ser Gln Leu Gln Ala Trp Leu Gln His 195 200 205 Tyr Gly Thr Ala Glu Val Asn Leu Gln Ser Gly Asn Asn Phe Asp Gly 210 215 220 Ser Ser Leu Asp Phe Leu Leu Pro Phe Tyr Asp Ser Glu Lys Met Leu 225 230 235 240 Ala Phe Gly Gln Val Gly Ala Arg Tyr Ile Asp Ser Arg Phe Thr Ala 245 250 255 Asn Leu Gly Ala Gly Gln Arg Phe Phe Leu Pro Ala Asn Met Leu Gly 260 265 270 Tyr Asn Val Phe Ile Asp Gln Asp Phe Ser Gly Asp Asn Thr Arg Leu 275 280 285 Gly Ile Gly Gly Glu Tyr Trp Arg Asp Tyr Phe Lys Ser Ser Val Asn 290 295 300 Gly Tyr Phe Arg Met Ser Gly Trp His Glu Ser Tyr Asn Lys Lys Asp 305 310 315 320 Tyr Asp Glu Arg Pro Ala Asn Gly Phe Asp Ile Arg Phe Asn Gly Tyr 325 330 335 Leu Pro Ser Tyr Pro Ala Leu Gly Ala Lys Leu Ile Tyr Glu Gln Tyr 340 345 350 Tyr Gly Asp Asn Val Ala Leu Phe Asn Ser Asp Lys Leu Gln Ser Asn 355 360 365 Pro Gly Ala Ala Thr Val Gly Val Asn Tyr Thr Pro Ile Pro Leu Val 370 375 380 Thr Met Gly Ile Asp Tyr Arg His Gly Thr Gly Asn Glu Asn Asp Leu 385 390 395 400 Leu Tyr Ser Met Gln Phe Arg Tyr Gln Phe Asp Lys Ser Trp Ser Gln 405 410 415 Gln Ile Glu Pro Gln Tyr Val Asn Glu Leu Arg Thr Leu Ser Gly Ser 420 425 430 Arg Tyr Asp Leu Val Gln Arg Asn Asn Asn Ile Ile Leu Glu Tyr Lys 435 440 445 Lys Gln Asp Ile Leu Ser Leu Asn Ile Pro His Asp Ile Asn Gly Thr 450 455 460 Glu His Ser Thr Gln Lys Ile Gln Leu Ile Val Lys Ser Lys Tyr Gly 465 470 475 480 Leu Asp Arg Ile Val Trp Asp Asp Ser Ala Leu Arg Ser Gln Gly Gly 485 490 495 Gln Ile Gln His Ser Gly Ser Gln Ser Ala Gln Asp Tyr Gln Ala Ile 500 505 510 Leu Pro Ala Tyr Val Gln Gly Gly Ser Asn Ile Tyr Lys Val Thr Ala 515 520 525 Arg Ala Tyr Tyr Arg Asn Gly Asn Ser Ser Asn Asn Val Gln Leu Thr 530 535 540 Ile Thr Val Leu Ser Asn Gly Gln Val Val Asp Gln Val Gly Val Thr 545 550 555 560 Asp Phe Thr Ala Asp Lys Thr Ser Ala Lys Ala Asp Asn Ala Asp Thr 565 570 575 Ile Thr Tyr Thr Ala Thr Val Lys Lys Asn Gly Val Ala Gln Ala Asn 580 585 590 Val Pro Val Ser Phe Asn Ile Val Ser Gly Thr Ala Thr Leu Gly Ala 595 600 605 Asn Ser Ala Lys Thr Asp Ala Asn Gly Lys Ala Thr Val Thr Leu Lys 610 615 620 Ser Ser Thr Pro Gly Gln Val Val Val Ser Ala Lys Thr Ala Glu Met 625 630 635 640 Thr Ser Ala Leu Asn Ala Ser Ala Val Ile Phe Phe Asp Gln Thr Lys 645 650 655 Ala Ser <210> SEQ ID NO 993 <400> SEQUENCE: 993 000 <210> SEQ ID NO 994 <400> SEQUENCE: 994 000 <210> SEQ ID NO 995 <400> SEQUENCE: 995 000 <210> SEQ ID NO 996 <400> SEQUENCE: 996 000 <210> SEQ ID NO 997 <400> SEQUENCE: 997 000 <210> SEQ ID NO 998 <400> SEQUENCE: 998 000 <210> SEQ ID NO 999 <400> SEQUENCE: 999 000 <210> SEQ ID NO 1000 <400> SEQUENCE: 1000 000 <210> SEQ ID NO 1001 <400> SEQUENCE: 1001 000 <210> SEQ ID NO 1002 <400> SEQUENCE: 1002 000 <210> SEQ ID NO 1003 <400> SEQUENCE: 1003 000 <210> SEQ ID NO 1004 <400> SEQUENCE: 1004 000 <210> SEQ ID NO 1005 <400> SEQUENCE: 1005 000 <210> SEQ ID NO 1006 <400> SEQUENCE: 1006 000 <210> SEQ ID NO 1007 <400> SEQUENCE: 1007 000 <210> SEQ ID NO 1008 <400> SEQUENCE: 1008 000 <210> SEQ ID NO 1009 <400> SEQUENCE: 1009 000 <210> SEQ ID NO 1010 <400> SEQUENCE: 1010 000 <210> SEQ ID NO 1011 <400> SEQUENCE: 1011 000 <210> SEQ ID NO 1012 <400> SEQUENCE: 1012 000 <210> SEQ ID NO 1013 <400> SEQUENCE: 1013 000 <210> SEQ ID NO 1014 <400> SEQUENCE: 1014 000 <210> SEQ ID NO 1015 <400> SEQUENCE: 1015 000 <210> SEQ ID NO 1016 <400> SEQUENCE: 1016 000 <210> SEQ ID NO 1017 <400> SEQUENCE: 1017 000 <210> SEQ ID NO 1018 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: Master Sequence <220> FEATURE: <221> NAME/KEY: modified_base <222> LOCATION: (13)..(15) <223> OTHER INFORMATION: a, c, g or t <220> FEATURE: <221> NAME/KEY: modified_base <222> LOCATION: (18)..(20) <223> OTHER INFORMATION: a, c, g or t <400> SEQUENCE: 1018 tctagagaaa gannngannn actagatg 28 <210> SEQ ID NO 1019 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61100 <400> SEQUENCE: 1019 tctagagaaa gaggggacaa actagatg 28 <210> SEQ ID NO 1020 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61101 <400> SEQUENCE: 1020 tctagagaaa gacaggaccc actagatg 28 <210> SEQ ID NO 1021 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61102 <400> SEQUENCE: 1021 tctagagaaa gatccgatgt actagatg 28 <210> SEQ ID NO 1022 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61103 <400> SEQUENCE: 1022 tctagagaaa gattagacaa actagatg 28 <210> SEQ ID NO 1023 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61104 <400> SEQUENCE: 1023 tctagagaaa gaagggacag actagatg 28 <210> SEQ ID NO 1024 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61105 <400> SEQUENCE: 1024 tctagagaaa gacatgacgt actagatg 28 <210> SEQ ID NO 1025 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61106 <400> SEQUENCE: 1025 tctagagaaa gataggagac actagatg 28 <210> SEQ ID NO 1026 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61107 <400> SEQUENCE: 1026 tctagagaaa gaagagactc actagatg 28 <210> SEQ ID NO 1027 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61108 <400> SEQUENCE: 1027 tctagagaaa gacgagatat actagatg 28 <210> SEQ ID NO 1028 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61109 <400> SEQUENCE: 1028 tctagagaaa gactggagac actagatg 28 <210> SEQ ID NO 1029 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61110 <400> SEQUENCE: 1029 tctagagaaa gaggcgaatt actagatg 28 <210> SEQ ID NO 1030 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61111 <400> SEQUENCE: 1030 tctagagaaa gaggcgatac actagatg 28 <210> SEQ ID NO 1031 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61112 <400> SEQUENCE: 1031 tctagagaaa gaggtgacat actagatg 28 <210> SEQ ID NO 1032 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61113 <400> SEQUENCE: 1032 tctagagaaa gagtggaaaa actagatg 28 <210> SEQ ID NO 1033 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61114 <400> SEQUENCE: 1033 tctagagaaa gatgagaaga actagatg 28 <210> SEQ ID NO 1034 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61115 <400> SEQUENCE: 1034 tctagagaaa gaagggatac actagatg 28 <210> SEQ ID NO 1035 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61116 <400> SEQUENCE: 1035 tctagagaaa gacatgaggc actagatg 28 <210> SEQ ID NO 1036 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61117 <400> SEQUENCE: 1036 tctagagaaa gacatgagtt actagatg 28 <210> SEQ ID NO 1037 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61118 <400> SEQUENCE: 1037 tctagagaaa gagacgaatc actagatg 28 <210> SEQ ID NO 1038 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61119 <400> SEQUENCE: 1038 tctagagaaa gatttgatat actagatg 28 <210> SEQ ID NO 1039 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61120 <400> SEQUENCE: 1039 tctagagaaa gacgcgagaa actagatg 28 <210> SEQ ID NO 1040 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61121 <400> SEQUENCE: 1040 tctagagaaa gagacgagtc actagatg 28 <210> SEQ ID NO 1041 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61122 <400> SEQUENCE: 1041 tctagagaaa gagaggagcc actagatg 28 <210> SEQ ID NO 1042 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61123 <400> SEQUENCE: 1042 tctagagaaa gagatgacta actagatg 28 <210> SEQ ID NO 1043 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61124 <400> SEQUENCE: 1043 tctagagaaa gagccgacat actagatg 28 <210> SEQ ID NO 1044 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61125 <400> SEQUENCE: 1044 tctagagaaa gagccgagtt actagatg 28 <210> SEQ ID NO 1045 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61126 <400> SEQUENCE: 1045 tctagagaaa gaggtgactc actagatg 28 <210> SEQ ID NO 1046 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61127 <400> SEQUENCE: 1046 tctagagaaa gagtggaact actagatg 28 <210> SEQ ID NO 1047 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61128 <400> SEQUENCE: 1047 tctagagaaa gataggactc actagatg 28 <210> SEQ ID NO 1048 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61129 <400> SEQUENCE: 1048 tctagagaaa gattggacgt actagatg 28 <210> SEQ ID NO 1049 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61130 <400> SEQUENCE: 1049 tctagagaaa gaaacgacat actagatg 28 <210> SEQ ID NO 1050 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61131 <400> SEQUENCE: 1050 tctagagaaa gaaccgaatt actagatg 28 <210> SEQ ID NO 1051 <400> SEQUENCE: 1051 000 <210> SEQ ID NO 1052 <400> SEQUENCE: 1052 000 <210> SEQ ID NO 1053 <400> SEQUENCE: 1053 000 <210> SEQ ID NO 1054 <400> SEQUENCE: 1054 000 <210> SEQ ID NO 1055 <400> SEQUENCE: 1055 000 <210> SEQ ID NO 1056 <400> SEQUENCE: 1056 000 <210> SEQ ID NO 1057 <400> SEQUENCE: 1057 000 <210> SEQ ID NO 1058 <400> SEQUENCE: 1058 000 <210> SEQ ID NO 1059 <400> SEQUENCE: 1059 000 <210> SEQ ID NO 1060 <400> SEQUENCE: 1060 000 <210> SEQ ID NO 1061 <400> SEQUENCE: 1061 000 <210> SEQ ID NO 1062 <400> SEQUENCE: 1062 000 <210> SEQ ID NO 1063 <400> SEQUENCE: 1063 000 <210> SEQ ID NO 1064 <400> SEQUENCE: 1064 000 <210> SEQ ID NO 1065 <400> SEQUENCE: 1065 000 <210> SEQ ID NO 1066 <400> SEQUENCE: 1066 000 <210> SEQ ID NO 1067 <400> SEQUENCE: 1067 000 <210> SEQ ID NO 1068 <400> SEQUENCE: 1068 000 <210> SEQ ID NO 1069 <400> SEQUENCE: 1069 000 <210> SEQ ID NO 1070 <400> SEQUENCE: 1070 000 <210> SEQ ID NO 1071 <400> SEQUENCE: 1071 000 <210> SEQ ID NO 1072 <400> SEQUENCE: 1072 000 <210> SEQ ID NO 1073 <400> SEQUENCE: 1073 000 <210> SEQ ID NO 1074 <400> SEQUENCE: 1074 000 <210> SEQ ID NO 1075 <400> SEQUENCE: 1075 000 <210> SEQ ID NO 1076 <400> SEQUENCE: 1076 000 <210> SEQ ID NO 1077 <400> SEQUENCE: 1077 000 <210> SEQ ID NO 1078 <400> SEQUENCE: 1078 000 <210> SEQ ID NO 1079 <400> SEQUENCE: 1079 000 <210> SEQ ID NO 1080 <400> SEQUENCE: 1080 000 <210> SEQ ID NO 1081 <400> SEQUENCE: 1081 000 <210> SEQ ID NO 1082 <400> SEQUENCE: 1082 000 <210> SEQ ID NO 1083 <400> SEQUENCE: 1083 000 <210> SEQ ID NO 1084 <400> SEQUENCE: 1084 000 <210> SEQ ID NO 1085 <400> SEQUENCE: 1085 000 <210> SEQ ID NO 1086 <400> SEQUENCE: 1086 000 <210> SEQ ID NO 1087 <400> SEQUENCE: 1087 000 <210> SEQ ID NO 1088 <400> SEQUENCE: 1088 000 <210> SEQ ID NO 1089 <400> SEQUENCE: 1089 000 <210> SEQ ID NO 1090 <400> SEQUENCE: 1090 000 <210> SEQ ID NO 1091 <400> SEQUENCE: 1091 000 <210> SEQ ID NO 1092 <400> SEQUENCE: 1092 000 <210> SEQ ID NO 1093 <400> SEQUENCE: 1093 000 <210> SEQ ID NO 1094 <400> SEQUENCE: 1094 000 <210> SEQ ID NO 1095 <400> SEQUENCE: 1095 000 <210> SEQ ID NO 1096 <400> SEQUENCE: 1096 000 <210> SEQ ID NO 1097 <400> SEQUENCE: 1097 000 <210> SEQ ID NO 1098 <400> SEQUENCE: 1098 000 <210> SEQ ID NO 1099 <400> SEQUENCE: 1099 000 <210> SEQ ID NO 1100 <400> SEQUENCE: 1100 000 <210> SEQ ID NO 1101 <400> SEQUENCE: 1101 000 <210> SEQ ID NO 1102 <400> SEQUENCE: 1102 000 <210> SEQ ID NO 1103 <400> SEQUENCE: 1103 000 <210> SEQ ID NO 1104 <400> SEQUENCE: 1104 000 <210> SEQ ID NO 1105 <400> SEQUENCE: 1105 000 <210> SEQ ID NO 1106 <400> SEQUENCE: 1106 000 <210> SEQ ID NO 1107 <400> SEQUENCE: 1107 000 <210> SEQ ID NO 1108 <400> SEQUENCE: 1108 000 <210> SEQ ID NO 1109 <400> SEQUENCE: 1109 000 <210> SEQ ID NO 1110 <400> SEQUENCE: 1110 000 <210> SEQ ID NO 1111 <400> SEQUENCE: 1111 000 <210> SEQ ID NO 1112 <400> SEQUENCE: 1112 000 <210> SEQ ID NO 1113 <400> SEQUENCE: 1113 000 <210> SEQ ID NO 1114 <400> SEQUENCE: 1114 000 <210> SEQ ID NO 1115 <400> SEQUENCE: 1115 000 <210> SEQ ID NO 1116 <400> SEQUENCE: 1116 000 <210> SEQ ID NO 1117 <400> SEQUENCE: 1117 000 <210> SEQ ID NO 1118 <400> SEQUENCE: 1118 000 <210> SEQ ID NO 1119 <400> SEQUENCE: 1119 000 <210> SEQ ID NO 1120 <400> SEQUENCE: 1120 000 <210> SEQ ID NO 1121 <400> SEQUENCE: 1121 000 <210> SEQ ID NO 1122 <400> SEQUENCE: 1122 000 <210> SEQ ID NO 1123 <400> SEQUENCE: 1123 000 <210> SEQ ID NO 1124 <400> SEQUENCE: 1124 000 <210> SEQ ID NO 1125 <400> SEQUENCE: 1125 000 <210> SEQ ID NO 1126 <400> SEQUENCE: 1126 000 <210> SEQ ID NO 1127 <400> SEQUENCE: 1127 000 <210> SEQ ID NO 1128 <400> SEQUENCE: 1128 000 <210> SEQ ID NO 1129 <400> SEQUENCE: 1129 000 <210> SEQ ID NO 1130 <400> SEQUENCE: 1130 000 <210> SEQ ID NO 1131 <400> SEQUENCE: 1131 000 <210> SEQ ID NO 1132 <400> SEQUENCE: 1132 000 <210> SEQ ID NO 1133 <400> SEQUENCE: 1133 000 <210> SEQ ID NO 1134 <400> SEQUENCE: 1134 000 <210> SEQ ID NO 1135 <211> LENGTH: 24 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1135 Met Phe Lys Ser Thr Leu Ala Ala Met Ala Ala Val Phe Ala Leu Ser 1 5 10 15 Ala Leu Ser Pro Ala Ala Met Ala 20 <210> SEQ ID NO 1136 <400> SEQUENCE: 1136 000 <210> SEQ ID NO 1137 <400> SEQUENCE: 1137 000 <210> SEQ ID NO 1138 <400> SEQUENCE: 1138 000 <210> SEQ ID NO 1139 <400> SEQUENCE: 1139 000 <210> SEQ ID NO 1140 <400> SEQUENCE: 1140 000 <210> SEQ ID NO 1141 <211> LENGTH: 72 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1141 atgtttaagt ctacacttgc agccatggcc gcagtcttcg cactgtcagc cttgagtcct 60 gctgcaatgg ca 72 <210> SEQ ID NO 1142 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1142 atgaagcagg cgcttcgcgt tgcgtttggg ttccttatcc tgtgggcatc cgtacttcac 60 gcc 63 <210> SEQ ID NO 1143 <211> LENGTH: 54 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1143 atgcgcgtac tgttattcct tctgttgtct ctttttatgt tgcccgcttt cagt 54 <210> SEQ ID NO 1144 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1144 atgaagaaga ctgccatcgc tattgccgtc gcccttgcgg gtttcgcaac cgtggcgcaa 60 gca 63 <210> SEQ ID NO 1145 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1145 atgaaatatc tgcttccaac ggctgctgct ggcctgttgc ttcttgccgc ccagcctgcg 60 atggct 66 <210> SEQ ID NO 1146 <400> SEQUENCE: 1146 000 <210> SEQ ID NO 1147 <400> SEQUENCE: 1147 000 <210> SEQ ID NO 1148 <400> SEQUENCE: 1148 000 <210> SEQ ID NO 1149 <400> SEQUENCE: 1149 000 <210> SEQ ID NO 1150 <400> SEQUENCE: 1150 000 <210> SEQ ID NO 1151 <400> SEQUENCE: 1151 000 <210> SEQ ID NO 1152 <400> SEQUENCE: 1152 000 <210> SEQ ID NO 1153 <400> SEQUENCE: 1153 000 <210> SEQ ID NO 1154 <400> SEQUENCE: 1154 000 <210> SEQ ID NO 1155 <400> SEQUENCE: 1155 000 <210> SEQ ID NO 1156 <400> SEQUENCE: 1156 000 <210> SEQ ID NO 1157 <211> LENGTH: 99 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1157 atggggtaca aaatgaacat tagctcgctt cgcaaagcat tcatttttat gggggctgtt 60 gcagctttaa gccttgtcaa tgcccagtca gcgcttgcc 99 <210> SEQ ID NO 1158 <211> LENGTH: 57 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1158 atgaaaaaga tttggctggc tcttgccggt ttagtcctgg cattcagcgc aagcgcg 57 <210> SEQ ID NO 1159 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1159 atgaaacaga gcacaatcgc tttagccttg ctgcctcttc ttttcacgcc tgtcacgaag 60 gca 63 <210> SEQ ID NO 1160 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1160 atgaagcagg ctctgcgcgt ggcatttggg ttcctgatct tatgggcgtc cgtcttacac 60 gca 63 <210> SEQ ID NO 1161 <211> LENGTH: 78 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1161 atgaaaatca agacgggggc acgcattctt gccttgagcg ccttgacaac gatgatgttc 60 agtgcaagtg cattagcg 78 <210> SEQ ID NO 1162 <211> LENGTH: 69 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1162 atgaataaga aagtcttgac attgtcggcg gtcatggcct cgatgttgtt cggggcagca 60 gcccacgca 69 <210> SEQ ID NO 1163 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1163 atgatgaagc gtaacatctt agccgttatt gtccccgcat tgcttgtggc cgggacggct 60 aacgca 66 <210> SEQ ID NO 1164 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1164 atgaagaaga ctgccatcgc tattgccgtc gcccttgcgg gtttcgcaac cgtggcgcaa 60 gca 63 <210> SEQ ID NO 1165 <211> LENGTH: 54 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1165 atgcgcgtgt tattgttctt gctgctgagc ttgtttatgt taccagcttt cagt 54 <210> SEQ ID NO 1166 <211> LENGTH: 75 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1166 atgatgatta ccttacgcaa gttgcccctt gcggtagccg ttgctgctgg tgtgatgtcc 60 gcgcaagcaa tggct 75 <210> SEQ ID NO 1167 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1167 atgaaatatc ttcttccaac ggctgctgct ggtttattgc ttcttgccgc ccagcctgcg 60 atggct 66 <210> SEQ ID NO 1168 <400> SEQUENCE: 1168 000 <210> SEQ ID NO 1169 <400> SEQUENCE: 1169 000 <210> SEQ ID NO 1170 <400> SEQUENCE: 1170 000 <210> SEQ ID NO 1171 <400> SEQUENCE: 1171 000 <210> SEQ ID NO 1172 <400> SEQUENCE: 1172 000 <210> SEQ ID NO 1173 <400> SEQUENCE: 1173 000 <210> SEQ ID NO 1174 <400> SEQUENCE: 1174 000 <210> SEQ ID NO 1175 <400> SEQUENCE: 1175 000 <210> SEQ ID NO 1176 <400> SEQUENCE: 1176 000 <210> SEQ ID NO 1177 <400> SEQUENCE: 1177 000 <210> SEQ ID NO 1178 <400> SEQUENCE: 1178 000 <210> SEQ ID NO 1179 <400> SEQUENCE: 1179 000 <210> SEQ ID NO 1180 <211> LENGTH: 33 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1180 Met Gly Tyr Lys Met Asn Ile Ser Ser Leu Arg Lys Ala Phe Ile Phe 1 5 10 15 Met Gly Ala Val Ala Ala Leu Ser Leu Val Asn Ala Gln Ser Ala Leu 20 25 30 Ala <210> SEQ ID NO 1181 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1181 Met Lys Lys Ile Trp Leu Ala Leu Ala Gly Leu Val Leu Ala Phe Ser 1 5 10 15 Ala Ser Ala <210> SEQ ID NO 1182 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1182 Met Lys Gln Ser Thr Ile Ala Leu Ala Leu Leu Pro Leu Leu Phe Thr 1 5 10 15 Pro Val Thr Lys Ala 20 <210> SEQ ID NO 1183 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1183 Met Lys Gln Ala Leu Arg Val Ala Phe Gly Phe Leu Ile Leu Trp Ala 1 5 10 15 Ser Val Leu His Ala 20 <210> SEQ ID NO 1184 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1184 Met Lys Ile Lys Thr Gly Ala Arg Ile Leu Ala Leu Ser Ala Leu Thr 1 5 10 15 Thr Met Met Phe Ser Ala Ser Ala Leu Ala 20 25 <210> SEQ ID NO 1185 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1185 Met Asn Lys Lys Val Leu Thr Leu Ser Ala Val Met Ala Ser Met Leu 1 5 10 15 Phe Gly Ala Ala Ala His Ala 20 <210> SEQ ID NO 1186 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1186 Met Thr Asn Ile Thr Lys Arg Ser Leu Val Ala Ala Gly Val Leu Ala 1 5 10 15 Ala Leu Met Ala Gly Asn Val Ala Leu Ala 20 25 <210> SEQ ID NO 1187 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1187 Met Lys Lys Thr Ala Ile Ala Ile Ala Val Ala Leu Ala Gly Phe Ala 1 5 10 15 Thr Val Ala Gln Ala 20 <210> SEQ ID NO 1188 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1188 Met Arg Val Leu Leu Phe Leu Leu Leu Ser Leu Phe Met Leu Pro Ala 1 5 10 15 Phe Ser <210> SEQ ID NO 1189 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1189 Met Met Ile Thr Leu Arg Lys Leu Pro Leu Ala Val Ala Val Ala Ala 1 5 10 15 Gly Val Met Ser Ala Gln Ala Met Ala 20 25 <210> SEQ ID NO 1190 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1190 Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala 1 5 10 15 Ala Gln Pro Ala Met Ala 20 <210> SEQ ID NO 1191 <400> SEQUENCE: 1191 000 <210> SEQ ID NO 1192 <400> SEQUENCE: 1192 000 <210> SEQ ID NO 1193 <400> SEQUENCE: 1193 000 <210> SEQ ID NO 1194 <400> SEQUENCE: 1194 000 <210> SEQ ID NO 1195 <400> SEQUENCE: 1195 000 <210> SEQ ID NO 1196 <400> SEQUENCE: 1196 000 <210> SEQ ID NO 1197 <400> SEQUENCE: 1197 000 <210> SEQ ID NO 1198 <400> SEQUENCE: 1198 000 <210> SEQ ID NO 1199 <400> SEQUENCE: 1199 000 <210> SEQ ID NO 1200 <400> SEQUENCE: 1200 000 <210> SEQ ID NO 1201 <400> SEQUENCE: 1201 000 <210> SEQ ID NO 1202 <400> SEQUENCE: 1202 000 <210> SEQ ID NO 1203 <400> SEQUENCE: 1203 000 <210> SEQ ID NO 1204 <400> SEQUENCE: 1204 000 <210> SEQ ID NO 1205 <400> SEQUENCE: 1205 000 <210> SEQ ID NO 1206 <400> SEQUENCE: 1206 000 <210> SEQ ID NO 1207 <400> SEQUENCE: 1207 000 <210> SEQ ID NO 1208 <400> SEQUENCE: 1208 000 <210> SEQ ID NO 1209 <400> SEQUENCE: 1209 000 <210> SEQ ID NO 1210 <400> SEQUENCE: 1210 000 <210> SEQ ID NO 1211 <400> SEQUENCE: 1211 000 <210> SEQ ID NO 1212 <400> SEQUENCE: 1212 000 <210> SEQ ID NO 1213 <400> SEQUENCE: 1213 000 <210> SEQ ID NO 1214 <400> SEQUENCE: 1214 000 <210> SEQ ID NO 1215 <400> SEQUENCE: 1215 000 <210> SEQ ID NO 1216 <400> SEQUENCE: 1216 000 <210> SEQ ID NO 1217 <400> SEQUENCE: 1217 000 <210> SEQ ID NO 1218 <211> LENGTH: 52 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1218 Met Lys Arg His Leu Asn Thr Ser Tyr Arg Leu Val Trp Asn His Ile 1 5 10 15 Thr Gly Ala Phe Val Val Ala Ser Glu Leu Ala Arg Ala Arg Gly Lys 20 25 30 Arg Ala Gly Val Ala Val Ala Leu Ser Leu Ala Ala Ala Thr Ser Leu 35 40 45 Pro Ala Leu Ala 50 <210> SEQ ID NO 1219 <211> LENGTH: 53 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1219 Met Asn Lys Ile Phe Lys Val Ile Trp Asn Pro Ala Thr Gly Ser Tyr 1 5 10 15 Thr Val Ala Ser Glu Thr Ala Lys Ser Arg Gly Lys Lys Ser Gly Arg 20 25 30 Ser Lys Leu Leu Ile Ser Ala Leu Val Ala Gly Gly Leu Leu Ser Ser 35 40 45 Phe Gly Ala Ser Ala 50 <210> SEQ ID NO 1220 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1220 Met Gln Leu Arg Lys Pro Ala Thr Ala Ile Leu Ala Leu Ala Leu Ser 1 5 10 15 Ala Gly Leu Ala Gln Ala 20 <210> SEQ ID NO 1221 <211> LENGTH: 40 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1221 Met Phe Trp Arg Asp Met Thr Leu Ser Val Trp Arg Lys Lys Thr Thr 1 5 10 15 Gly Leu Lys Thr Lys Lys Arg Leu Leu Ala Leu Val Leu Ala Ala Ala 20 25 30 Leu Cys Ser Ser Pro Val Trp Ala 35 40 <210> SEQ ID NO 1222 <211> LENGTH: 159 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1222 atgaacaaga ttttcaaggt tatctggaac cccgcgacag gcagctacac tgtggcctcc 60 gaaaccgcta agtcgcgcgg caagaagtca ggacgttcaa agctgcttat ttctgcttta 120 gtagccggag gattactttc tagctttgga gcctcggca 159 <210> SEQ ID NO 1223 <211> LENGTH: 57 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1223 atgaaaaaaa tctggctggc attagcaggc ttagtcctgg cctttagtgc ctcggca 57 <210> SEQ ID NO 1224 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1224 atgcagttgc gcaagcctgc cacggcaatt ttagcattag ctctttctgc gggcttggcc 60 caggca 66 <210> SEQ ID NO 1225 <211> LENGTH: 120 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1225 atgttctggc gcgacatgac actgagcgtt tggcgtaaaa aaacaacggg actgaaaacc 60 aaaaagcgtt tgttagccct tgtcctggcg gcagccctgt gctcgtcccc ggtatgggca 120 <210> SEQ ID NO 1226 <211> LENGTH: 99 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1226 atgggataca agatgaacat ttcatcactt cgcaaagctt ttatcttcat gggtgccgtt 60 gctgctctgt cactggtcaa tgctcaatcg gccctggca 99 <210> SEQ ID NO 1227 <211> LENGTH: 78 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1227 atgaagatta aaacaggcgc tcgtattttg gccctgtctg cgcttacgac tatgatgttt 60 agtgcctcgg ccctggca 78 <210> SEQ ID NO 1228 <211> LENGTH: 78 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1228 atgacgaata tcactaaacg tagccttgtg gccgcggggg tcttggctgc attgatggct 60 ggcaatgttg ctctggca 78 <210> SEQ ID NO 1229 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1229 atgaaatatc tgttgcccac ggctgccgcg ggtctgctgc tgctggcagc gcaaccggct 60 atggca 66 <210> SEQ ID NO 1230 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1230 atgaagcaaa gtacgatcgc ccttgcgctg ttgccccttc ttttcacgcc cgtcaccaag 60 gca 63 <210> SEQ ID NO 1231 <400> SEQUENCE: 1231 000 <210> SEQ ID NO 1232 <400> SEQUENCE: 1232 000 <210> SEQ ID NO 1233 <400> SEQUENCE: 1233 000 <210> SEQ ID NO 1234 <400> SEQUENCE: 1234 000 <210> SEQ ID NO 1235 <400> SEQUENCE: 1235 000 <210> SEQ ID NO 1236 <400> SEQUENCE: 1236 000 <210> SEQ ID NO 1237 <400> SEQUENCE: 1237 000 <210> SEQ ID NO 1238 <400> SEQUENCE: 1238 000 <210> SEQ ID NO 1239 <400> SEQUENCE: 1239 000 <210> SEQ ID NO 1240 <400> SEQUENCE: 1240 000 <210> SEQ ID NO 1241 <400> SEQUENCE: 1241 000 <210> SEQ ID NO 1242 <400> SEQUENCE: 1242 000 <210> SEQ ID NO 1243 <400> SEQUENCE: 1243 000 <210> SEQ ID NO 1244 <400> SEQUENCE: 1244 000 <210> SEQ ID NO 1245 <400> SEQUENCE: 1245 000 <210> SEQ ID NO 1246 <400> SEQUENCE: 1246 000 <210> SEQ ID NO 1247 <400> SEQUENCE: 1247 000 <210> SEQ ID NO 1248 <400> SEQUENCE: 1248 000 <210> SEQ ID NO 1249 <400> SEQUENCE: 1249 000 <210> SEQ ID NO 1250 <211> LENGTH: 24 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1250 ggaaaatttt tttaaaaaaa aaac 24 <210> SEQ ID NO 1251 <400> SEQUENCE: 1251 000 <210> SEQ ID NO 1252 <400> SEQUENCE: 1252 000 <210> SEQ ID NO 1253 <211> LENGTH: 57 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1253 atgaagaaaa tttggctggc acttgccggt ttggtattag cgttttccgc ctcggca 57 <210> SEQ ID NO 1254 <211> LENGTH: 522 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 1254 Met Gln Pro Trp His Gly Lys Ala Met Gln Arg Ala Ser Glu Ala Gly 1 5 10 15 Ala Thr Ala Pro Lys Ala Ser Ala Arg Asn Ala Arg Gly Ala Pro Met 20 25 30 Asp Pro Thr Glu Ser Pro Ala Ala Pro Glu Ala Ala Leu Pro Lys Ala 35 40 45 Gly Lys Phe Gly Pro Ala Arg Lys Ser Gly Ser Arg Gln Lys Lys Ser 50 55 60 Ala Pro Asp Thr Gln Glu Arg Pro Pro Val Arg Ala Thr Gly Ala Arg 65 70 75 80 Ala Lys Lys Ala Pro Gln Arg Ala Gln Asp Thr Gln Pro Ser Asp Ala 85 90 95 Thr Ser Ala Pro Gly Ala Glu Gly Leu Glu Pro Pro Ala Ala Arg Glu 100 105 110 Pro Ala Leu Ser Arg Ala Gly Ser Cys Arg Gln Arg Gly Ala Arg Cys 115 120 125 Ser Thr Lys Pro Arg Pro Pro Pro Gly Pro Trp Asp Val Pro Ser Pro 130 135 140 Gly Leu Pro Val Ser Ala Pro Ile Leu Val Arg Arg Asp Ala Ala Pro 145 150 155 160 Gly Ala Ser Lys Leu Arg Ala Val Leu Glu Lys Leu Lys Leu Ser Arg 165 170 175 Asp Asp Ile Ser Thr Ala Ala Gly Met Val Lys Gly Val Val Asp His 180 185 190 Leu Leu Leu Arg Leu Lys Cys Asp Ser Ala Phe Arg Gly Val Gly Leu 195 200 205 Leu Asn Thr Gly Ser Tyr Tyr Glu His Val Lys Ile Ser Ala Pro Asn 210 215 220 Glu Phe Asp Val Met Phe Lys Leu Glu Val Pro Arg Ile Gln Leu Glu 225 230 235 240 Glu Tyr Ser Asn Thr Arg Ala Tyr Tyr Phe Val Lys Phe Lys Arg Asn 245 250 255 Pro Lys Glu Asn Pro Leu Ser Gln Phe Leu Glu Gly Glu Ile Leu Ser 260 265 270 Ala Ser Lys Met Leu Ser Lys Phe Arg Lys Ile Ile Lys Glu Glu Ile 275 280 285 Asn Asp Ile Lys Asp Thr Asp Val Ile Met Lys Arg Lys Arg Gly Gly 290 295 300 Ser Pro Ala Val Thr Leu Leu Ile Ser Glu Lys Ile Ser Val Asp Ile 305 310 315 320 Thr Leu Ala Leu Glu Ser Lys Ser Ser Trp Pro Ala Ser Thr Gln Glu 325 330 335 Gly Leu Arg Ile Gln Asn Trp Leu Ser Ala Lys Val Arg Lys Gln Leu 340 345 350 Arg Leu Lys Pro Phe Tyr Leu Val Pro Lys His Ala Lys Glu Gly Asn 355 360 365 Gly Phe Gln Glu Glu Thr Trp Arg Leu Ser Phe Ser His Ile Glu Lys 370 375 380 Glu Ile Leu Asn Asn His Gly Lys Ser Lys Thr Cys Cys Glu Asn Lys 385 390 395 400 Glu Glu Lys Cys Cys Arg Lys Asp Cys Leu Lys Leu Met Lys Tyr Leu 405 410 415 Leu Glu Gln Leu Lys Glu Arg Phe Lys Asp Lys Lys His Leu Asp Lys 420 425 430 Phe Ser Ser Tyr His Val Lys Thr Ala Phe Phe His Val Cys Thr Gln 435 440 445 Asn Pro Gln Asp Ser Gln Trp Asp Arg Lys Asp Leu Gly Leu Cys Phe 450 455 460 Asp Asn Cys Val Thr Tyr Phe Leu Gln Cys Leu Arg Thr Glu Lys Leu 465 470 475 480 Glu Asn Tyr Phe Ile Pro Glu Phe Asn Leu Phe Ser Ser Asn Leu Ile 485 490 495 Asp Lys Arg Ser Lys Glu Phe Leu Thr Lys Gln Ile Glu Tyr Glu Arg 500 505 510 Asn Asn Glu Phe Pro Val Phe Asp Glu Phe 515 520 <210> SEQ ID NO 1255 <211> LENGTH: 1569 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 1255 atgcaaccat ggcatggtaa ggcaatgcaa cgtgcatctg aggctggagc taccgcgccc 60 aaagcttcag cacggaacgc gcgcggtgct ccgatggatc cgacggagag ccctgctgca 120 ccggaagccg ctctgccaaa agcgggtaaa ttcgggccgg cgcggaaatc aggctcacgc 180 cagaaaaaga gtgctccgga tacacaggaa cgtccgcctg taagagctac cggcgcgcgc 240 gctaaaaaag cccctcagcg tgcgcaggat acccaaccat cggatgcaac gagcgcaccg 300 ggggcggagg gccttgagcc tcctgctgcg cgtgagccgg ccctctctcg cgcagggagt 360 tgccgccaac gaggcgcacg ctgctcgacg aaaccgcggc cccctccggg tccgtgggat 420 gttccatcgc caggcctgcc ggtttctgcg cctattctcg ttcgccgcga cgcggctcct 480 ggcgcttcga aactgagagc tgtcttagag aaactgaaac tctcgcggga tgatatatct 540 actgcggcag ggatggtcaa aggtgttgtg gatcatctcc tgttacgtct taagtgcgat 600 tcggccttcc gaggtgttgg ccttttaaac actgggtcat actatgagca cgttaagatc 660 agcgcgccga acgagttcga cgttatgttt aagcttgaag tccctcgcat acagctggaa 720 gaatactcca atacacgagc atattatttt gttaaattca aacgaaaccc caaagagaac 780 cctctttcac agtttctgga gggagaaatt ctgtctgcga gtaagatgct ctcgaagttc 840 cgaaaaatca ttaaagagga aatcaacgac atcaaagaca ctgatgttat catgaagagg 900 aaacgtgggg gctcaccggc ggtaacactg ctgatttcgg aaaagatctc agttgatatt 960 actttggcgc tcgaatcaaa atcatcgtgg ccggcgagta cacaggaagg gctccgtatt 1020 cagaattggc tgtctgcgaa agtccgcaaa caactgcgtt tgaaaccatt ttatttagtg 1080 ccaaaacacg cgaaagaagg caacggtttc caggaggaga cgtggcgact gtcatttagc 1140 cacatagaaa aggaaatatt aaataatcac gggaaaagta agacgtgctg cgagaataaa 1200 gaagagaagt gctgcaggaa agattgtctg aaactgatga aatacctgtt ggagcagctg 1260 aaagagaggt ttaaagataa gaagcatctg gacaaatttt cttcatatca cgttaaaacc 1320 gcattcttcc acgtatgcac acagaatccg caggactcac agtgggatcg gaaagatctg 1380 ggcctgtgct ttgacaactg cgtcacatat ttcttgcagt gcttgaggac tgaaaaattg 1440 gaaaactact tcattcccga gttcaattta ttcagtagta acctgatcga caagcgtagc 1500 aaagaattcc tgacgaagca gatcgaatac gaaagaaata acgaattccc ggtgtttgat 1560 gaattttaa 1569 <210> SEQ ID NO 1256 <400> SEQUENCE: 1256 000 <210> SEQ ID NO 1257 <211> LENGTH: 273 <212> TYPE: PRT <213> ORGANISM: Listeria monocytogenes <400> SEQUENCE: 1257 Met Asp Phe Ser Asn Met Ser Ile Leu His Tyr Leu Ala Asn Ile Val 1 5 10 15 Asp Ile Leu Val Val Trp Phe Val Ile Tyr Lys Val Ile Met Leu Ile 20 25 30 Arg Gly Thr Lys Ala Val Gln Leu Leu Lys Gly Ile Phe Ile Ile Ile 35 40 45 Ala Val Lys Leu Leu Ser Gly Phe Phe Gly Leu Gln Thr Val Glu Trp 50 55 60 Ile Thr Asp Gln Met Leu Thr Trp Gly Phe Leu Ala Ile Ile Ile Ile 65 70 75 80 Phe Gln Pro Glu Leu Arg Arg Ala Leu Glu Thr Leu Gly Arg Gly Asn 85 90 95 Ile Phe Thr Arg Tyr Gly Ser Arg Ile Glu Arg Glu Gln His His Leu 100 105 110 Ile Glu Ser Ile Glu Lys Ser Thr Gln Tyr Met Ala Lys Arg Arg Ile 115 120 125 Gly Ala Leu Ile Ser Val Ala Arg Asp Thr Gly Met Asp Asp Tyr Ile 130 135 140 Glu Thr Gly Ile Pro Leu Asn Ala Lys Ile Ser Ser Gln Leu Leu Ile 145 150 155 160 Asn Ile Phe Ile Pro Asn Thr Pro Leu His Asp Gly Ala Val Ile Ile 165 170 175 Lys Gly Asn Glu Ile Ala Ser Ala Ala Ser Tyr Leu Pro Leu Ser Asp 180 185 190 Ser Pro Phe Leu Ser Lys Glu Leu Gly Thr Arg His Arg Ala Ala Leu 195 200 205 Gly Ile Ser Glu Val Thr Asp Ser Ile Thr Ile Val Val Ser Glu Glu 210 215 220 Thr Gly Gly Ile Ser Leu Thr Lys Gly Gly Glu Leu Phe Arg Asp Val 225 230 235 240 Ser Glu Glu Glu Leu His Lys Ile Leu Leu Lys Glu Leu Val Thr Val 245 250 255 Thr Ala Lys Lys Pro Ser Ile Phe Ser Lys Trp Lys Gly Gly Lys Ser 260 265 270 Glu <210> SEQ ID NO 1258 <211> LENGTH: 822 <212> TYPE: DNA <213> ORGANISM: Listeria monocytogenes <400> SEQUENCE: 1258 atggactttt ccaacatgag tatccttcac tatttagcga atattgtaga cattttggtg 60 gtttggttcg taatttacaa ggttatcatg cttatccgcg gcacgaaagc cgtccagctg 120 ttgaagggga ttttcattat tattgccgtc aagttactta gcggcttctt cggattgcag 180 acagtggaat ggattactga tcaaatgctg acttggggtt tcttagccat tatcattatc 240 tttcaaccgg aattgcgtcg tgccctggag actttggggc gtggcaatat ctttacccgc 300 tatggatcac gcattgagcg tgaacaacac caccttattg agtctattga aaagtccacg 360 caatacatgg cgaagcgtcg cattggagct ttgatctctg tggctcgtga tacaggcatg 420 gacgactaca tcgagactgg cattccgctt aatgcgaaaa tctcatcgca attattgatt 480 aatatcttca tccccaatac ccctcttcac gatggcgcag tgatcattaa aggtaacgag 540 atcgcgagcg ctgccagtta tctgccattg tccgactcgc cgtttctttc taaggagctg 600 ggaactcgcc atcgtgccgc attagggatt tccgaggtga cagattcaat cacaatcgtt 660 gtcagcgagg aaacaggtgg gatttccctt acgaagggag gcgaactgtt ccgtgatgta 720 tccgaagaag aattgcataa gattttgctt aaagagctgg tgactgtcac agctaaaaaa 780 ccaagcattt tctccaaatg gaaaggaggt aagtccgagt ga 822 <210> SEQ ID NO 1259 <400> SEQUENCE: 1259 000 <210> SEQ ID NO 1260 <211> LENGTH: 403 <212> TYPE: PRT <213> ORGANISM: Kingella denitrificans <400> SEQUENCE: 1260 Met Ser Asp Tyr Thr Asn Asn Leu His Arg Val Phe Val Asp Gln Lys 1 5 10 15 Ile Gly Phe Lys Lys Lys Ile Thr Pro Thr Glu Gln Asp Leu Asn Phe 20 25 30 Phe Asn Gln Val Lys Lys Asp Val Lys Ser His Leu Lys Thr Lys Ile 35 40 45 Lys Glu Phe Leu Glu Gln Gln Gly Ile Ala Asn Ile Ala Pro Lys Phe 50 55 60 Arg Ile Gln Gly Ser Trp Ala Tyr Gly Thr Cys Asn Leu Pro Ala Lys 65 70 75 80 Gln Asp Gln Glu Met Asp Phe Asp Tyr Gly Val Tyr Leu Pro Val Arg 85 90 95 Ala Phe Glu Gly Phe Asn Pro Asp Ala Gly Ala Ser Glu Gln Ala Gln 100 105 110 Asn Tyr Phe Glu Gln Val Glu Leu Met Val Glu Asp Leu Cys His Gln 115 120 125 His Lys Trp Gln Leu Asp Thr Ser Ala Pro Ser Ser Cys Ile Arg Ile 130 135 140 Lys Ile Arg Ser Asn Ala His Met Asp Ile Pro Leu Tyr Ala Val Pro 145 150 155 160 Asp Asp Met Phe Asp Ser Leu Glu Glu Arg Asn Glu Leu Gln Val Ser 165 170 175 Leu Gly Thr Thr Thr Ala Ile Asp Lys Ser Leu Asn Tyr Ser Glu Trp 180 185 190 Ala Leu Glu Asp Phe Asn Ile Arg Ser Phe Ala Glu Glu Ser Leu Met 195 200 205 Asp Lys Asn Ile Arg Met Ile His Met Ala Arg Arg Asp Gly Thr Trp 210 215 220 Gln Lys Ser Asp Cys Glu Leu Ile Arg Lys Trp Phe Ala Asp Lys Leu 225 230 235 240 Lys Ser Leu Glu Asn Asn Gly Gln Gln Leu Arg Ala Ile Cys Arg Tyr 245 250 255 Leu Lys Ala Trp Arg Asp Trp Gln Phe Ala Asp Lys Ser Phe Gln Pro 260 265 270 Ser Ser Ile Leu Leu Met Ile Ile Ala Cys Lys Tyr Tyr Gln Tyr His 275 280 285 Gln His Arg Asp Asp Leu Ala Leu Leu Ser Val Leu Glu Lys Leu Pro 290 295 300 Asn Ala Leu Asn Asp Asn Val Tyr Glu Asn Ile Glu Glu His Glu Ser 305 310 315 320 Glu Asp Phe Asn Arg Met Glu Glu Tyr Glu Arg Val Glu Ala Ser Gln 325 330 335 Tyr Ala Asp Ala Leu Tyr Gln Ser Phe Met Ala Ser Leu Asn Asn Leu 340 345 350 Asp Lys Thr Lys Val Leu Asn Phe Ile Thr Asn Glu Trp Gly Asp Arg 355 360 365 Ile Pro Gln Asp Glu Asn Leu Ile Glu Thr Ser Pro Gln Ser Ile Phe 370 375 380 Asp Thr Pro Pro Leu Ala Gln Ser Asn Ile Thr Gln Gln Val Pro Leu 385 390 395 400 Arg Gln Gly <210> SEQ ID NO 1261 <211> LENGTH: 403 <212> TYPE: PRT <213> ORGANISM: Neisseria bacilliformis <400> SEQUENCE: 1261 Met Ser His Tyr Thr Asn Asn Leu His Arg Ile Phe Val Asp Arg Glu 1 5 10 15 Ile Gly Phe Lys Lys Glu Ile Thr Pro Thr Glu Leu Asp Leu Asp Phe 20 25 30 Phe Asn Asn Val Lys Lys Val Val Lys Ser His Leu Lys Thr Lys Ile 35 40 45 Lys Glu Phe Leu Glu Gln Gln Gly Leu Ala Ser Ile Thr Pro Lys Phe 50 55 60 Arg Ile Gln Gly Ser Trp Ala Tyr Gly Thr Cys Asn Leu Pro Ala Lys 65 70 75 80 Gln Gly Gln Glu Met Asp Phe Asp Tyr Gly Val Tyr Leu Pro Val Arg 85 90 95 Ala Phe Asp Gly Phe Asn Pro Asp Ala Gly Ala Ser Glu Gln Ala Lys 100 105 110 Asn Tyr Phe Glu Gln Val Glu Leu Met Met Gly Asp Leu Cys Glu Gln 115 120 125 His Asp Trp Leu Leu Asp Thr Ser Ala Pro Ser Ser Cys Ile Arg Ile 130 135 140 Lys Ile Arg Asn Asn Ala His Met Asp Ile Pro Leu Tyr Ala Val Pro 145 150 155 160 Asp Asp Met Phe Asp Ser Leu Glu Glu Arg Asn Glu Leu Gln Val Ser 165 170 175 Leu Gly Ser Ala Thr Ala Ile His Glu Ser Leu Asn Tyr Ser Lys Trp 180 185 190 Val Phe Glu Asp Phe Asn Ile Arg Ser Phe Ala Glu Glu Ser Leu Met 195 200 205 Asp Lys Asn Ile Arg Met Ile His Met Ala Arg Arg Asp Gly Thr Trp 210 215 220 Gln Glu Ser Asp Cys Glu Leu Ile Arg Lys Trp Phe Ala Asp Lys Leu 225 230 235 240 Lys Ser Leu Glu Asn Asn Gly Gln Gln Leu Arg Ala Ile Cys Arg Tyr 245 250 255 Leu Lys Ala Trp Arg Asp Trp Gln Phe Ala Asp Lys Ser Phe Gln Pro 260 265 270 Ser Ser Ile Leu Leu Met Ile Ile Ala Cys Lys Tyr Tyr Gln Tyr Tyr 275 280 285 Gln His Arg Asp Asp Leu Ala Leu Leu Ser Val Leu Glu Lys Leu Pro 290 295 300 Asn Ala Leu Ser Gly Asn Val Tyr Glu Asn Ile Glu Glu His Glu Ser 305 310 315 320 Glu Asp Phe Asn Arg Met Lys Glu Gly Glu Arg Val Glu Ala Met Gln 325 330 335 Tyr Ala Asp Ala Leu Tyr Gln Asn Phe Met Ala Ser Leu Asn Asn Phe 340 345 350 Asp Lys Thr Lys Ala Leu Lys Phe Ile Thr Asn Glu Trp Gly Asn Arg 355 360 365 Ile Pro Gln Asp Glu Asp Leu Ile Glu Thr Ser Arg Gln Ala Ile Phe 370 375 380 Asp Thr Pro Pro Leu Val Gln Pro Asn Ile Thr Pro Gln Ala Pro Leu 385 390 395 400 Arg Gln Gly <210> SEQ ID NO 1262 <211> LENGTH: 468 <212> TYPE: PRT <213> ORGANISM: Verminephrobacter eiseniae <400> SEQUENCE: 1262 Met Gly Gln Ala Ser Lys Leu Phe Asn Gly Asn Thr Asp Gln Thr Leu 1 5 10 15 Ile Gly Arg Val Thr Pro Thr Thr Glu Gln Arg Glu Phe Leu Gln Gln 20 25 30 Gln Trp Asn Asp Leu Ala Asp His Leu Lys Gln Ala Leu Ala Lys His 35 40 45 Gly Tyr Thr Ile Ser Thr Trp Leu Gln Gly Ser Tyr Lys Tyr Ala Thr 50 55 60 Leu Ile Lys Pro Val His Leu Gly Glu Glu Tyr Asp Val Asp Val Gly 65 70 75 80 Leu Tyr Phe Glu Trp Asn Asp Asp Gln Asp Ala Glu Pro Thr Pro Lys 85 90 95 Gln Leu Arg Asp Trp Val Gln Ala Glu Leu Leu Glu Tyr Glu Lys Ala 100 105 110 Cys Glu Glu Leu Lys Lys Val Glu Val Pro Pro Lys Glu Arg Cys Ser 115 120 125 Arg Ala Ser Tyr Ile Gln Gln Phe His Ile Asp Thr Pro Val Tyr His 130 135 140 Leu Asn Thr Asp Ser Asp Val Arg Arg Leu Ala Cys Leu Ser Gly Lys 145 150 155 160 Trp Glu His Ser Asp Pro Lys Lys Leu Tyr Lys Trp Phe Lys Glu Ala 165 170 175 Val Ser Gly Asp Asp Arg Asp Gln Leu Arg Arg Leu Val Arg Tyr Leu 180 185 190 Lys Ala Trp Ala Ala Val Ser Phe Asp Asp Ala Pro Gly Ser Arg Pro 195 200 205 Ser Ser Ile Phe Leu Thr Val Ile Ala Thr Glu Ala Tyr Gln Asp Leu 210 215 220 Trp Ala Gln Arg Leu Leu Gly Leu Ala Asp Asp Asp Ala Leu Leu Ala 225 230 235 240 Val Ile Lys Lys Met His Asp Arg Leu Phe Asp Asp Arg Lys Val Glu 245 250 255 Asn Pro Val Asp Lys Asn Glu Asp Leu Asn Arg Met Thr Ala Glu Ala 260 265 270 Trp Asp Gly Phe Leu Pro Arg Leu Ala Ala Leu Gln Asp Ile Ala Glu 275 280 285 Arg Ala Gly Asp Ala Lys Asp Glu Ala Ser Ala Ala Leu Ile Trp Ser 290 295 300 Glu Ala Phe Ser Phe Leu Met Pro Leu Pro Glu Thr Asp Gln Val Glu 305 310 315 320 Ile Val Asp Glu Gly Ser Gly Arg Ala Val Met Gln Leu Pro Glu Ile 325 330 335 Glu Val Lys Val Cys Thr Gly Thr Pro Pro Arg Pro Val Ala Thr Tyr 340 345 350 Arg Asn Glu Val Pro Gly Val Ala Lys Asp Cys Met Leu Ser Phe Ala 355 360 365 Ile Val Asn Pro His Val Val Pro Glu Phe Ala Thr Val Glu Trp Thr 370 375 380 Val Arg Asn Glu Gly Gln Glu Ala Asp Gln Arg Ser Asp Leu Gly His 385 390 395 400 Arg Arg Val Gly Met Arg Leu Leu Ser Val Glu Glu His Thr Ala Tyr 405 410 415 Val Gly Arg His Phe Met Asp Cys Val Val Arg Leu Asn Gly Gln Val 420 425 430 Tyr Ala Val Arg Arg Val Pro Val Thr Ile Arg Asp Val Gln His Val 435 440 445 Ala Arg Asn Pro Pro Arg Pro Pro Tyr Thr Lys Leu Arg Ser Leu Phe 450 455 460 Arg Arg Arg Arg 465 <210> SEQ ID NO 1263 <211> LENGTH: 1213 <212> TYPE: DNA <213> ORGANISM: Kingella denitrificans <400> SEQUENCE: 1263 atgtcagact acactaataa cttgcatcgc gtctttgttg accaaaaaat tgggttcaag 60 aagaaaatca ctcctaccga gcaagatctg aactttttca atcaggtcaa gaaagatgta 120 aagtcccacc ttaagaccaa aatcaaggaa tttcttgagc aacagggaat cgcgaacatt 180 gctccgaagt tccgtattca gggatcgtgg gcttacggga catgtaattt gcccgcaaaa 240 caggaccagg agatggattt cgattacggg gtatatctgc cagtacgtgc cttcgagggg 300 ttcaacccag acgcaggcgc gtctgagcag gctcaaaact attttgaaca ggtcgagttg 360 atggttgaag atctgtgcca ccagcataaa tggcagctgg acacgtctgc cccttcgtcc 420 tgtatccgca ttaaaattcg cagcaacgct catatggaca ttcctttata tgccgtcccg 480 gatgatatgt tcgattctct tgaagagcgc aatgagttac aagtatcact gggcacgaca 540 acggctatcg ataagtcact gaattacagc gagtgggcac tggaggactt taatatccgc 600 tcattcgccg aagaaagttt aatggataag aacattcgca tgatccacat ggcgcgtcgt 660 gacgggactt ggcaaaagtc ggattgcgag ctgattcgca aatggttcgc agacaaactg 720 aagagcttgg agaataacgg gcaacagctg cgtgcgatct gtcgttacct taaggcgtgg 780 cgcgattggc aattcgctga caagtcgttt caaccatcct ctatcttgtt aatgattatc 840 gcgtgcaaat attatcaata ccatcaacac cgtgacgatt tagcactttt atccgtgctt 900 gaaaagttgc caaacgcttt aaacgataat gtttatgaga atattgaaga acacgaatcc 960 gaagacttta accgtatgga agagtatgaa cgcgttgagg cgtcgcagta tgccgacgcg 1020 ttgtaccaga gtttcatggc ctccttaaac aatttggaca aaactaaggt tttaaatttt 1080 atcactaatg agtgggggga tcgcattcca caagacgaga acttaatcga gacatctcct 1140 caatcaattt tcgatactcc ccccttggca caaagcaata tcacgcaaca agtgcccttg 1200 cgccagggtt aas 1213 <210> SEQ ID NO 1264 <211> LENGTH: 1212 <212> TYPE: DNA <213> ORGANISM: Neisseria bacilliformis <400> SEQUENCE: 1264 atgtctcact acaccaataa tcttcatcgt atcttcgtag atcgtgaaat tggttttaag 60 aaagagatta ctccgacaga gctggatctt gacttcttca acaacgtcaa aaaagtagtt 120 aagagccacc ttaaaaccaa aatcaaggag tttcttgaac agcaagggct ggcgagtatt 180 actcctaagt ttcgtatcca gggaagctgg gcgtacggaa catgtaacct tccagccaag 240 cagggtcagg aaatggactt cgattatggc gtttatcttc ctgtccgcgc ctttgatgga 300 tttaatcctg atgcaggtgc ctcagaacaa gctaagaatt acttcgaaca ggtggagctt 360 atgatgggtg acctgtgcga gcagcatgac tggttgttgg acacatccgc gccctcttcg 420 tgtattcgca tcaaaatccg caataatgcc catatggaca ttcctttata tgcagttcca 480 gacgatatgt tcgatagcct ggaggaacgt aacgaattac aggtttcctt gggatcagcg 540 acagctattc acgaatcgct gaattattca aagtgggttt ttgaggattt taacatccgc 600 tcttttgctg aggaatccct gatggacaaa aatatccgca tgatccacat ggcccgccgt 660 gacggaactt ggcaggagtc tgattgtgag ttgattcgca aatggtttgc tgacaagttg 720 aaatcccttg agaataatgg tcagcagctt cgtgcaattt gtcgctatct taaagcctgg 780 cgcgattggc aattcgcaga taagtctttt caaccctcca gtatcctgtt gatgatcatt 840 gcgtgtaagt actatcagta ctaccaacat cgtgacgacc tggcactgct gtccgtgctg 900 gagaaattgc ccaacgcttt gtctgggaac gtctatgaga atattgagga acatgagtct 960 gaggacttta accgtatgaa agagggcgag cgtgtagaag caatgcaata tgcggacgcg 1020 ttataccaaa acttcatggc gtctcttaac aattttgata aaacgaaggc gctgaaattc 1080 atcactaatg aatggggaaa tcgtatccca caagatgaag acttaatcga aacgtctcgt 1140 caggcaattt ttgacacacc acccttagtt caacccaaca tcactccaca ggccccactt 1200 cgccaggggt aa 1212 <210> SEQ ID NO 1265 <211> LENGTH: 1407 <212> TYPE: DNA <213> ORGANISM: Verminephrobacter eiseniae <400> SEQUENCE: 1265 atgggacagg cgtctaagtt atttaatggt aatacagatc aaactttaat tggccgcgtg 60 acgcccacta ccgaacaacg cgagttttta caacagcagt ggaatgatct ggcagatcac 120 ttgaagcaag ccctggcaaa acacggttat acaatttcga catggcttca gggttcttac 180 aaatacgcga ctcttattaa gcctgtgcat ctgggtgaag agtatgacgt agatgtaggg 240 ttgtactttg agtggaacga tgaccaggat gcggagccca cgcctaagca gctgcgtgat 300 tgggtgcaag cggagttgtt agagtatgag aaggcttgtg aggaacttaa gaaagttgag 360 gtgccgccga aagaacgctg ttctcgcgca tcatacatcc aacaatttca cattgacaca 420 ccagtttatc atctgaacac ggactccgac gtgcgccgtc ttgcttgcct tagtggaaag 480 tgggagcatt ctgatccgaa aaagttatac aagtggttta aagaagcagt atccggggat 540 gatcgtgacc aattacgccg tcttgtacgt tacttaaagg cctgggctgc ggtttccttt 600 gatgacgcac cgggatcccg cccatctagc atttttctta cggttattgc tactgaagcc 660 tatcaggact tgtgggcaca acgtttactg ggattagctg acgatgacgc tttgctggca 720 gtgattaaaa agatgcacga ccgccttttc gatgaccgca aggtcgagaa tcccgtagat 780 aaaaacgaag acttaaatcg catgacggct gaagcgtggg acggttttct gccccgcttg 840 gcggcacttc aagacattgc ggaacgcgcc ggagatgcta aggatgaggc gtcagccgca 900 ttgatctgga gcgaagcgtt tagttttttg atgcccttgc cggaaactga tcaggtagaa 960 atcgtagacg aaggctcagg ccgtgccgtc atgcaattgc cagaaattga ggtaaaggtc 1020 tgcactggca cgccaccccg cccagtcgca acgtatcgta atgaggtccc aggagtagca 1080 aaagactgca tgttgtcctt tgcgattgtc aatccacatg tggttccgga gtttgccacg 1140 gtggagtgga ctgtgcgtaa tgagggacag gaggcggacc agcgtagtga tttagggcac 1200 cgtcgcgtcg ggatgcgttt gttgagtgta gaggaacata cggcatatgt cggtcgtcac 1260 tttatggatt gtgtagtccg tctgaacggg caagtttacg ctgtccgtcg cgtacccgtt 1320 accattcgcg acgttcagca cgtcgcccgc aatcccccac gtccacctta cacaaaactg 1380 cgcagtttat tccgccgccg tcgctaa 1407 <210> SEQ ID NO 1266 <400> SEQUENCE: 1266 000 <210> SEQ ID NO 1267 <400> SEQUENCE: 1267 000 <210> SEQ ID NO 1268 <211> LENGTH: 621 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1268 ctaacgtttg aattttgcgt aacgttcgcg agcaatctct aaagtgctat tacgtacacg 60 ctcaaaacgt tccttatcct tctgccataa cgaacgcacc gcaagaccac gcacgctgtt 120 aaaaatcaac cacaaaatgt cctcggcatc gtcacgggat aatccacgcg acaccagaac 180 gcccaaccac atatcctcga ccacaaaacg gttgcgctct accgtgcgtt ggataccctc 240 acgcagagct ggatcacgat cagcggccac aatcagatca aggctaattg aaaagtcgtc 300 atccaagaaa aactcagcgg catcatcaag catttgctga atcacatcat cttccggttt 360 taacttagcc aggcgagcac ggctgcgctc ggtgatctgc tcatacagcc actcaaacgt 420 agcaagcaac agttctaatt tggtgggaaa atggtgtgac tgggcgccac gagacacccc 480 cgcggcgccc ggtacatccg caatacgaaa acccgcgtat cccttctcgc gtaatacacc 540 aagcgccgcc gcgatcagtt taccttgtgt ttccatcgca cgttcggctt gagtacggcg 600 cttgggcgac atgattacca t 621 <210> SEQ ID NO 1269 <211> LENGTH: 206 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1269 Met Val Ile Met Ser Pro Lys Arg Arg Thr Gln Ala Glu Arg Ala Met 1 5 10 15 Glu Thr Gln Gly Lys Leu Ile Ala Ala Ala Leu Gly Val Leu Arg Glu 20 25 30 Lys Gly Tyr Ala Gly Phe Arg Ile Ala Asp Val Pro Gly Ala Ala Gly 35 40 45 Val Ser Arg Gly Ala Gln Ser His His Phe Pro Thr Lys Leu Glu Leu 50 55 60 Leu Leu Ala Thr Phe Glu Trp Leu Tyr Glu Gln Ile Thr Glu Arg Ser 65 70 75 80 Arg Ala Arg Leu Ala Lys Leu Lys Pro Glu Asp Asp Val Ile Gln Gln 85 90 95 Met Leu Asp Asp Ala Ala Glu Phe Phe Leu Asp Asp Asp Phe Ser Ile 100 105 110 Ser Leu Asp Leu Ile Val Ala Ala Asp Arg Asp Pro Ala Leu Arg Glu 115 120 125 Gly Ile Gln Arg Thr Val Glu Arg Asn Arg Phe Val Val Glu Asp Met 130 135 140 Trp Leu Gly Val Leu Val Ser Arg Gly Leu Ser Arg Asp Asp Ala Glu 145 150 155 160 Asp Ile Leu Trp Leu Ile Phe Asn Ser Val Arg Gly Leu Ala Val Arg 165 170 175 Ser Leu Trp Gln Lys Asp Lys Glu Arg Phe Glu Arg Val Arg Asn Ser 180 185 190 Thr Leu Glu Ile Ala Arg Glu Arg Tyr Ala Lys Phe Lys Arg 195 200 205 <210> SEQ ID NO 1270 <211> LENGTH: 123 <212> TYPE: DNA <213> ORGANISM: Escherichia coli <400> SEQUENCE: 1270 taacaccgtg cgtgttgact attttacctc tggcggtgat aatggttgca acaaacagac 60 aatctggtct gtttgtatta tgttaaccag cacactggcg gccgcttact agaaataatt 120 ttg 123 <210> SEQ ID NO 1271 <211> LENGTH: 161 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1271 taacaccgtg cgtgttgact attttacctc tggcggtgat aatggttgca acaaacagac 60 aatctggtct gtttgtatta tgttaaccag cacactggcg gccgcttact agaaataatt 120 ttggccgcat cccacgctaa ctaatataaa ggaggtttta a 161 <210> SEQ ID NO 1272 <400> SEQUENCE: 1272 000 <210> SEQ ID NO 1273 <211> LENGTH: 79 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1273 tgtatttatc aatattgttt gctccgttat cgttattaac aagtcatcaa taaagccatc 60 acgagtacca tagaggatc 79 <210> SEQ ID NO 1274 <211> LENGTH: 117 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1274 tgtatttatc aatattgttt gctccgttat cgttattaac aagtcatcaa taaagccatc 60 acgagtacca tagaggatcg ccgcatccca cgctaactaa tataaaggag gttttaa 117 <210> SEQ ID NO 1275 <400> SEQUENCE: 1275 000 <210> SEQ ID NO 1276 <400> SEQUENCE: 1276 000 <210> SEQ ID NO 1277 <400> SEQUENCE: 1277 000 <210> SEQ ID NO 1278 <211> LENGTH: 903 <212> TYPE: DNA <213> ORGANISM: Pseudomonas sp. <400> SEQUENCE: 1278 tcaatctgta aacaaatcga acatcagttg acgaagccag atattggcca aatccttatg 60 gtatttagcg tgccagaaca tattaatggc aatctcggga agcactaccg gatgaggcag 120 agcggacaag ccgaaaggtt cgacacagca atccgctaag cggatcggca ctgttgccag 180 caggtcagta cgttgaagaa tatggccaac ggctgcgaaa tggggcactt ccagacgaat 240 atcacgacgg atgcctacac gggtcatata cgtgtccact tcaccgtggc ctgtgcctgc 300 tgcaataaca cgtacatgtc cataactaca aaagcgttca agcgtcaatg gctcacgggt 360 aacggggtgg tccttgcggc acaaacaaac gtagtggttt tgcagtaaac ggcgttggaa 420 gaagcctgtt tgaaggttgg gcagaagccc caccgccaaa tcgacagttc cattttgcaa 480 cgcctgcatt aatgacatag acgaatcgcg gacagtagaa atgacgcagt tcggtgcttg 540 atgggcaagt acgtccatca ggcgaggcat gaaataaatc tccccaatat ccgtcattgc 600 cagggtgaaa gtacgctccg aagtaagggg gtcaaagctc tcatgatgtt gtaaagcgtt 660 acgaagggcg tgcatggcac tggtgacagg ctcggccaag tgtgcggcgt atggcgttgg 720 ttccatccct tggtgagtac ggacgaacaa cggatcttgt aacgatgtac gaaggcgttt 780 taatgcgtta gaaactgcgg gttgagtaag cccaagattt tctgcggtga tggagacgcg 840 acgatctacc agcagctgat taaagacaac taacaggtta aggtccagat cacgcaattc 900 cat 903 <210> SEQ ID NO 1279 <400> SEQUENCE: 1279 000 <210> SEQ ID NO 1280 <211> LENGTH: 300 <212> TYPE: PRT <213> ORGANISM: Pseudomonas sp. <400> SEQUENCE: 1280 Met Glu Leu Arg Asp Leu Asp Leu Asn Leu Leu Val Val Phe Asn Gln 1 5 10 15 Leu Leu Val Asp Arg Arg Val Ser Ile Thr Ala Glu Asn Leu Gly Leu 20 25 30 Thr Gln Pro Ala Val Ser Asn Ala Leu Lys Arg Leu Arg Thr Ser Leu 35 40 45 Gln Asp Pro Leu Phe Val Arg Thr His Gln Gly Met Glu Pro Thr Pro 50 55 60 Tyr Ala Ala His Leu Ala Glu Pro Val Thr Ser Ala Met His Ala Leu 65 70 75 80 Arg Asn Ala Leu Gln His His Glu Ser Phe Asp Pro Leu Thr Ser Glu 85 90 95 Arg Thr Phe Thr Leu Ala Met Thr Asp Ile Gly Glu Ile Tyr Phe Met 100 105 110 Pro Arg Leu Met Asp Val Leu Ala His Gln Ala Pro Asn Cys Val Ile 115 120 125 Ser Thr Val Arg Asp Ser Ser Met Ser Leu Met Gln Ala Leu Gln Asn 130 135 140 Gly Thr Val Asp Leu Ala Val Gly Leu Leu Pro Asn Leu Gln Thr Gly 145 150 155 160 Phe Phe Gln Arg Arg Leu Leu Gln Asn His Tyr Val Cys Leu Cys Arg 165 170 175 Lys Asp His Pro Val Thr Arg Glu Pro Leu Thr Leu Glu Arg Phe Cys 180 185 190 Ser Tyr Gly His Val Arg Val Ile Ala Ala Gly Thr Gly His Gly Glu 195 200 205 Val Asp Thr Tyr Met Thr Arg Val Gly Ile Arg Arg Asp Ile Arg Leu 210 215 220 Glu Val Pro His Phe Ala Ala Val Gly His Ile Leu Gln Arg Thr Asp 225 230 235 240 Leu Leu Ala Thr Val Pro Ile Arg Leu Ala Asp Cys Cys Val Glu Pro 245 250 255 Phe Gly Leu Ser Ala Leu Pro His Pro Val Val Leu Pro Glu Ile Ala 260 265 270 Ile Asn Met Phe Trp His Ala Lys Tyr His Lys Asp Leu Ala Asn Ile 275 280 285 Trp Leu Arg Gln Leu Met Phe Asp Leu Phe Thr Asp 290 295 300 <210> SEQ ID NO 1281 <211> LENGTH: 164 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1281 agttgttctt attggtggtg ttgctttatg gttgcatcgt agtaaatggt tgtaacaaaa 60 gcaatttttc cggctgtctg tatacaaaaa cgccgcaaag tttgagcgaa gtcaataaac 120 tctctaccca ttcagggcaa tatctctctt ggatccaaag tgaa 164 <210> SEQ ID NO 1282 <211> LENGTH: 201 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1282 agttgttctt attggtggtg ttgctttatg gttgcatcgt agtaaatggt tgtaacaaaa 60 gcaatttttc cggctgtctg tatacaaaaa cgccgcaaag tttgagcgaa gtcaataaac 120 tctctaccca ttcagggcaa tatctctctt ggatccaaag tgaacccgca tcccacgcta 180 actaatataa ggggggcaag a 201 <210> SEQ ID NO 1283 <400> SEQUENCE: 1283 000 <210> SEQ ID NO 1284 <211> LENGTH: 1023 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1284 agttgttctt attggtggtg ttgctttatg gttgcatcgt agtaaatggt tgtaacaaaa 60 gcaatttttc cggctgtctg tatacaaaaa cgccgcaaag tttgagcgaa gtcaataaac 120 tctctaccca ttcagggcaa tatctctctt ggatccaaag tgaacccgca tcccacgcta 180 actaatataa ggggggcaag aatggacttt tccaacatga gtatccttca ctatttagcg 240 aatattgtag acattttggt ggtttggttc gtaatttaca aggttatcat gcttatccgc 300 ggcacgaaag ccgtccagct gttgaagggg attttcatta ttattgccgt caagttactt 360 agcggcttct tcggattgca gacagtggaa tggattactg atcaaatgct gacttggggt 420 ttcttagcca ttatcattat ctttcaaccg gaattgcgtc gtgccctgga gactttgggg 480 cgtggcaata tctttacccg ctatggatca cgcattgagc gtgaacaaca ccaccttatt 540 gagtctattg aaaagtccac gcaatacatg gcgaagcgtc gcattggagc tttgatctct 600 gtggctcgtg atacaggcat ggacgactac atcgagactg gcattccgct taatgcgaaa 660 atctcatcgc aattattgat taatatcttc atccccaata cccctcttca cgatggcgca 720 gtgatcatta aaggtaacga gatcgcgagc gctgccagtt atctgccatt gtccgactcg 780 ccgtttcttt ctaaggagct gggaactcgc catcgtgccg cattagggat ttccgaggtg 840 acagattcaa tcacaatcgt tgtcagcgag gaaacaggtg ggatttccct tacgaaggga 900 ggcgaactgt tccgtgatgt atccgaagaa gaattgcata agattttgct taaagagctg 960 gtgactgtca cagctaaaaa accaagcatt ttctccaaat ggaaaggagg taagtccgag 1020 tga 1023 <210> SEQ ID NO 1285 <400> SEQUENCE: 1285 000 <210> SEQ ID NO 1286 <400> SEQUENCE: 1286 000 <210> SEQ ID NO 1287 <400> SEQUENCE: 1287 000 <210> SEQ ID NO 1288 <400> SEQUENCE: 1288 000 <210> SEQ ID NO 1289 <400> SEQUENCE: 1289 000 <210> SEQ ID NO 1290 <400> SEQUENCE: 1290 000 <210> SEQ ID NO 1291 <400> SEQUENCE: 1291 000 <210> SEQ ID NO 1292 <400> SEQUENCE: 1292 000 <210> SEQ ID NO 1293 <400> SEQUENCE: 1293 000 <210> SEQ ID NO 1294 <400> SEQUENCE: 1294 000 <210> SEQ ID NO 1295 <400> SEQUENCE: 1295 000 <210> SEQ ID NO 1296 <400> SEQUENCE: 1296 000 <210> SEQ ID NO 1297 <400> SEQUENCE: 1297 000 <210> SEQ ID NO 1298 <400> SEQUENCE: 1298 000 <210> SEQ ID NO 1299 <400> SEQUENCE: 1299 000 <210> SEQ ID NO 1300 <400> SEQUENCE: 1300 000 <210> SEQ ID NO 1301 <400> SEQUENCE: 1301 000 <210> SEQ ID NO 1302 <400> SEQUENCE: 1302 000 <210> SEQ ID NO 1303 <400> SEQUENCE: 1303 000 <210> SEQ ID NO 1304 <400> SEQUENCE: 1304 000 <210> SEQ ID NO 1305 <400> SEQUENCE: 1305 000 <210> SEQ ID NO 1306 <400> SEQUENCE: 1306 000 <210> SEQ ID NO 1307 <400> SEQUENCE: 1307 000 <210> SEQ ID NO 1308 <400> SEQUENCE: 1308 000 <210> SEQ ID NO 1309 <400> SEQUENCE: 1309 000 <210> SEQ ID NO 1310 <400> SEQUENCE: 1310 000 <210> SEQ ID NO 1311 <400> SEQUENCE: 1311 000 <210> SEQ ID NO 1312 <400> SEQUENCE: 1312 000 <210> SEQ ID NO 1313 <400> SEQUENCE: 1313 000 <210> SEQ ID NO 1314 <400> SEQUENCE: 1314 000 <210> SEQ ID NO 1315 <400> SEQUENCE: 1315 000 <210> SEQ ID NO 1316 <400> SEQUENCE: 1316 000 <210> SEQ ID NO 1317 <400> SEQUENCE: 1317 000 <210> SEQ ID NO 1318 <400> SEQUENCE: 1318 000 <210> SEQ ID NO 1319 <400> SEQUENCE: 1319 000 <210> SEQ ID NO 1320 <400> SEQUENCE: 1320 000 <210> SEQ ID NO 1321 <400> SEQUENCE: 1321 000 <210> SEQ ID NO 1322 <400> SEQUENCE: 1322 000 <210> SEQ ID NO 1323 <400> SEQUENCE: 1323 000 <210> SEQ ID NO 1324 <400> SEQUENCE: 1324 000 <210> SEQ ID NO 1325 <400> SEQUENCE: 1325 000 <210> SEQ ID NO 1326 <400> SEQUENCE: 1326 000 <210> SEQ ID NO 1327 <400> SEQUENCE: 1327 000 <210> SEQ ID NO 1328 <400> SEQUENCE: 1328 000 <210> SEQ ID NO 1329 <400> SEQUENCE: 1329 000 <210> SEQ ID NO 1330 <400> SEQUENCE: 1330 000 <210> SEQ ID NO 1331 <400> SEQUENCE: 1331 000 <210> SEQ ID NO 1332 <400> SEQUENCE: 1332 000 <210> SEQ ID NO 1333 <400> SEQUENCE: 1333 000 <210> SEQ ID NO 1334 <400> SEQUENCE: 1334 000 <210> SEQ ID NO 1335 <400> SEQUENCE: 1335 000 <210> SEQ ID NO 1336 <400> SEQUENCE: 1336 000 <210> SEQ ID NO 1337 <400> SEQUENCE: 1337 000 <210> SEQ ID NO 1338 <400> SEQUENCE: 1338 000 <210> SEQ ID NO 1339 <400> SEQUENCE: 1339 000 <210> SEQ ID NO 1340 <400> SEQUENCE: 1340 000 <210> SEQ ID NO 1341 <400> SEQUENCE: 1341 000 <210> SEQ ID NO 1342 <400> SEQUENCE: 1342 000 <210> SEQ ID NO 1343 <400> SEQUENCE: 1343 000 <210> SEQ ID NO 1344 <400> SEQUENCE: 1344 000 <210> SEQ ID NO 1345 <400> SEQUENCE: 1345 000 <210> SEQ ID NO 1346 <400> SEQUENCE: 1346 000 <210> SEQ ID NO 1347 <400> SEQUENCE: 1347 000 <210> SEQ ID NO 1348 <400> SEQUENCE: 1348 000 <210> SEQ ID NO 1349 <400> SEQUENCE: 1349 000 <210> SEQ ID NO 1350 <400> SEQUENCE: 1350 000 <210> SEQ ID NO 1351 <400> SEQUENCE: 1351 000 <210> SEQ ID NO 1352 <400> SEQUENCE: 1352 000 <210> SEQ ID NO 1353 <400> SEQUENCE: 1353 000 <210> SEQ ID NO 1354 <400> SEQUENCE: 1354 000 <210> SEQ ID NO 1355 <400> SEQUENCE: 1355 000 <210> SEQ ID NO 1356 <400> SEQUENCE: 1356 000 <210> SEQ ID NO 1357 <400> SEQUENCE: 1357 000 <210> SEQ ID NO 1358 <400> SEQUENCE: 1358 000 <210> SEQ ID NO 1359 <400> SEQUENCE: 1359 000 <210> SEQ ID NO 1360 <400> SEQUENCE: 1360 000 <210> SEQ ID NO 1361 <400> SEQUENCE: 1361 000 <210> SEQ ID NO 1362 <400> SEQUENCE: 1362 000 <210> SEQ ID NO 1363 <400> SEQUENCE: 1363 000 <210> SEQ ID NO 1364 <400> SEQUENCE: 1364 000 <210> SEQ ID NO 1365 <400> SEQUENCE: 1365 000 <210> SEQ ID NO 1366 <400> SEQUENCE: 1366 000 <210> SEQ ID NO 1367 <400> SEQUENCE: 1367 000 <210> SEQ ID NO 1368 <400> SEQUENCE: 1368 000 <210> SEQ ID NO 1369 <400> SEQUENCE: 1369 000 <210> SEQ ID NO 1370 <400> SEQUENCE: 1370 000 <210> SEQ ID NO 1371 <400> SEQUENCE: 1371 000 <210> SEQ ID NO 1372 <400> SEQUENCE: 1372 000 <210> SEQ ID NO 1373 <400> SEQUENCE: 1373 000 <210> SEQ ID NO 1374 <400> SEQUENCE: 1374 000 <210> SEQ ID NO 1375 <400> SEQUENCE: 1375 000 <210> SEQ ID NO 1376 <400> SEQUENCE: 1376 000 <210> SEQ ID NO 1377 <400> SEQUENCE: 1377 000 <210> SEQ ID NO 1378 <400> SEQUENCE: 1378 000 <210> SEQ ID NO 1379 <400> SEQUENCE: 1379 000 <210> SEQ ID NO 1380 <400> SEQUENCE: 1380 000 <210> SEQ ID NO 1381 <400> SEQUENCE: 1381 000 <210> SEQ ID NO 1382 <400> SEQUENCE: 1382 000 <210> SEQ ID NO 1383 <400> SEQUENCE: 1383 000 <210> SEQ ID NO 1384 <400> SEQUENCE: 1384 000 <210> SEQ ID NO 1385 <400> SEQUENCE: 1385 000 <210> SEQ ID NO 1386 <400> SEQUENCE: 1386 000 <210> SEQ ID NO 1387 <400> SEQUENCE: 1387 000 <210> SEQ ID NO 1388 <400> SEQUENCE: 1388 000 <210> SEQ ID NO 1389 <400> SEQUENCE: 1389 000 <210> SEQ ID NO 1390 <400> SEQUENCE: 1390 000 <210> SEQ ID NO 1391 <400> SEQUENCE: 1391 000 <210> SEQ ID NO 1392 <400> SEQUENCE: 1392 000 <210> SEQ ID NO 1393 <400> SEQUENCE: 1393 000 <210> SEQ ID NO 1394 <400> SEQUENCE: 1394 000 <210> SEQ ID NO 1395 <400> SEQUENCE: 1395 000 <210> SEQ ID NO 1396 <400> SEQUENCE: 1396 000 <210> SEQ ID NO 1397 <400> SEQUENCE: 1397 000 <210> SEQ ID NO 1398 <400> SEQUENCE: 1398 000 <210> SEQ ID NO 1399 <400> SEQUENCE: 1399 000 <210> SEQ ID NO 1400 <400> SEQUENCE: 1400 000 <210> SEQ ID NO 1401 <400> SEQUENCE: 1401 000 <210> SEQ ID NO 1402 <400> SEQUENCE: 1402 000 <210> SEQ ID NO 1403 <400> SEQUENCE: 1403 000 <210> SEQ ID NO 1404 <400> SEQUENCE: 1404 000 <210> SEQ ID NO 1405 <400> SEQUENCE: 1405 000 <210> SEQ ID NO 1406 <400> SEQUENCE: 1406 000 <210> SEQ ID NO 1407 <400> SEQUENCE: 1407 000 <210> SEQ ID NO 1408 <400> SEQUENCE: 1408 000 <210> SEQ ID NO 1409 <400> SEQUENCE: 1409 000 <210> SEQ ID NO 1410 <400> SEQUENCE: 1410 000 <210> SEQ ID NO 1411 <400> SEQUENCE: 1411 000 <210> SEQ ID NO 1412 <400> SEQUENCE: 1412 000 <210> SEQ ID NO 1413 <400> SEQUENCE: 1413 000 <210> SEQ ID NO 1414 <400> SEQUENCE: 1414 000 <210> SEQ ID NO 1415 <400> SEQUENCE: 1415 000 <210> SEQ ID NO 1416 <400> SEQUENCE: 1416 000 <210> SEQ ID NO 1417 <400> SEQUENCE: 1417 000 <210> SEQ ID NO 1418 <400> SEQUENCE: 1418 000 <210> SEQ ID NO 1419 <400> SEQUENCE: 1419 000 <210> SEQ ID NO 1420 <400> SEQUENCE: 1420 000 <210> SEQ ID NO 1421 <400> SEQUENCE: 1421 000 <210> SEQ ID NO 1422 <400> SEQUENCE: 1422 000 <210> SEQ ID NO 1423 <400> SEQUENCE: 1423 000 <210> SEQ ID NO 1424 <400> SEQUENCE: 1424 000 <210> SEQ ID NO 1425 <400> SEQUENCE: 1425 000 <210> SEQ ID NO 1426 <400> SEQUENCE: 1426 000 <210> SEQ ID NO 1427 <400> SEQUENCE: 1427 000 <210> SEQ ID NO 1428 <400> SEQUENCE: 1428 000 <210> SEQ ID NO 1429 <400> SEQUENCE: 1429 000 <210> SEQ ID NO 1430 <400> SEQUENCE: 1430 000 <210> SEQ ID NO 1431 <400> SEQUENCE: 1431 000 <210> SEQ ID NO 1432 <400> SEQUENCE: 1432 000 <210> SEQ ID NO 1433 <400> SEQUENCE: 1433 000 <210> SEQ ID NO 1434 <400> SEQUENCE: 1434 000 <210> SEQ ID NO 1435 <400> SEQUENCE: 1435 000 <210> SEQ ID NO 1436 <400> SEQUENCE: 1436 000 <210> SEQ ID NO 1437 <400> SEQUENCE: 1437 000 <210> SEQ ID NO 1438 <400> SEQUENCE: 1438 000 <210> SEQ ID NO 1439 <400> SEQUENCE: 1439 000 <210> SEQ ID NO 1440 <400> SEQUENCE: 1440 000 <210> SEQ ID NO 1441 <400> SEQUENCE: 1441 000 <210> SEQ ID NO 1442 <400> SEQUENCE: 1442 000 <210> SEQ ID NO 1443 <211> LENGTH: 42 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1443 tcgacattta tcccttgcgg cgaatactta cagccatagc aa 42 <210> SEQ ID NO 1444 <211> LENGTH: 49 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1444 ggcgcgcctt gacaattaat catccggctc ctaggatgtg tggagggac 49 <210> SEQ ID NO 1445 <211> LENGTH: 50 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1445 ggcgcgcctt gacatcagga aaatttttct gtataataga ttcatctcaa 50 <210> SEQ ID NO 1446 <211> LENGTH: 51 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1446 ggcgcgcctt gacataaagt ctaacctata ggatacttac agccatacaa g 51 <210> SEQ ID NO 1447 <400> SEQUENCE: 1447 000 <210> SEQ ID NO 1448 <400> SEQUENCE: 1448 000 <210> SEQ ID NO 1449 <211> LENGTH: 915 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1449 ccgcgtgctg cacaaccgcg tacacaagct gcagcccagg ccgacgcagt atccacgaac 60 acaaattcag cgttgagtga tgctatggct tcaactcaat caattctttt ggacaccggc 120 gcatatttaa ctcgccatat cgcccaaaag tctcgtgcgg atgcagaaaa aaatagcgtg 180 tggatgtcga atactgggta tgggcgcgac tacgcctctg cgcagtaccg ccgtttcagc 240 agcaaacgca cccagactca aatcgggatc gatcgtagtc ttagtgagaa tatgcagatt 300 ggcggagttc tgacttattc cgactctcaa catacgttcg accaggcagg gggcaagaat 360 acgtttgtac aggccaatct ttacggaaag tactacttga atgatgcctg gtatgtcgct 420 ggggacattg gcgcagggag cttgcgttcc cgccttcaaa cgcaacaaaa ggcgaatttc 480 aatcgcacca gcattcagac tggccttaca cttgggaata cacttaagat taatcaattt 540 gagattgtgc ccagtgctgg gattcgttat agtcgtttat ccagcgcaga ctataagtta 600 ggcgacgact ctgtgaaagt tagctcaatg gccgtgaaga cgttgacggc tggtttggat 660 ttcgcctatc gctttaaagt tggaaatctg accgtgaagc cgctgctttc ggccgcttat 720 tttgcaaact acggcaaggg cggcgttaat gtcggtggta agagtttcgc ctataaagct 780 gacaatcagc agcaatattc ggccggcgtc gcgttgttgt atcgcaacgt gactttaaat 840 gtaaacggct ccatcacaaa gggcaagcag ttggagaagc aaaagtcagg ccaaatcaag 900 attcaaatcc gtttc 915 <210> SEQ ID NO 1450 <211> LENGTH: 696 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1450 atgttaatca atagaaacat tgtcgccctt tttgccctgc cattcatggc gagtgcgacc 60 gcttccgagt taagcatagg ggccggcgct gcgtataatg agagtcctta ccgtggctat 120 aatgaaaaca caaaggcaat cccccttatc tcgtatgaag gcgacacctt ctatgtacgt 180 cagactacat taggtttcat cttaagccag tccgagaaaa acgagttatc gctgacagct 240 tcatggatgc cattggaatt cgacccgaca gataatgatg attatgcgat gcagcagctg 300 gacaaacggg attcgacagc tatggccggc gtggcttggt atcaccacga gcggtgggga 360 actgtcaaag cttccgccgc cgctgacgtg ttagacaaca gcaatggctg ggtgggggaa 420 ttaagcgtgt tccataagat gcagataggt agattatccc ttacaccggc tttgggagtc 480 ctgtattatg atgagaactt ttccgactat tattatggga tttctgagtc tgaaagtcgt 540 cggagcggtc ttgcgtcgta ctcggcgcaa gacgcgtggg tgccttatgt atctttgaca 600 gcgaagtatc caataggcga gcacgtggta ttgatggcaa gtgctggtta ttccgagttg 660 cccgaagaaa ttactgacag tcctatgata gaccgt 696 <210> SEQ ID NO 1451 <400> SEQUENCE: 1451 000 <210> SEQ ID NO 1452 <400> SEQUENCE: 1452 000 <210> SEQ ID NO 1453 <400> SEQUENCE: 1453 000 <210> SEQ ID NO 1454 <400> SEQUENCE: 1454 000 <210> SEQ ID NO 1455 <400> SEQUENCE: 1455 000 <210> SEQ ID NO 1456 <400> SEQUENCE: 1456 000 <210> SEQ ID NO 1457 <400> SEQUENCE: 1457 000 <210> SEQ ID NO 1458 <400> SEQUENCE: 1458 000 <210> SEQ ID NO 1459 <400> SEQUENCE: 1459 000 <210> SEQ ID NO 1460 <400> SEQUENCE: 1460 000 <210> SEQ ID NO 1461 <400> SEQUENCE: 1461 000 <210> SEQ ID NO 1462 <400> SEQUENCE: 1462 000 <210> SEQ ID NO 1463 <400> SEQUENCE: 1463 000 <210> SEQ ID NO 1464 <211> LENGTH: 305 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1464 Pro Arg Ala Ala Gln Pro Arg Thr Gln Ala Ala Ala Gln Ala Asp Ala 1 5 10 15 Val Ser Thr Asn Thr Asn Ser Ala Leu Ser Asp Ala Met Ala Ser Thr 20 25 30 Gln Ser Ile Leu Leu Asp Thr Gly Ala Tyr Leu Thr Arg His Ile Ala 35 40 45 Gln Lys Ser Arg Ala Asp Ala Glu Lys Asn Ser Val Trp Met Ser Asn 50 55 60 Thr Gly Tyr Gly Arg Asp Tyr Ala Ser Ala Gln Tyr Arg Arg Phe Ser 65 70 75 80 Ser Lys Arg Thr Gln Thr Gln Ile Gly Ile Asp Arg Ser Leu Ser Glu 85 90 95 Asn Met Gln Ile Gly Gly Val Leu Thr Tyr Ser Asp Ser Gln His Thr 100 105 110 Phe Asp Gln Ala Gly Gly Lys Asn Thr Phe Val Gln Ala Asn Leu Tyr 115 120 125 Gly Lys Tyr Tyr Leu Asn Asp Ala Trp Tyr Val Ala Gly Asp Ile Gly 130 135 140 Ala Gly Ser Leu Arg Ser Arg Leu Gln Thr Gln Gln Lys Ala Asn Phe 145 150 155 160 Asn Arg Thr Ser Ile Gln Thr Gly Leu Thr Leu Gly Asn Thr Leu Lys 165 170 175 Ile Asn Gln Phe Glu Ile Val Pro Ser Ala Gly Ile Arg Tyr Ser Arg 180 185 190 Leu Ser Ser Ala Asp Tyr Lys Leu Gly Asp Asp Ser Val Lys Val Ser 195 200 205 Ser Met Ala Val Lys Thr Leu Thr Ala Gly Leu Asp Phe Ala Tyr Arg 210 215 220 Phe Lys Val Gly Asn Leu Thr Val Lys Pro Leu Leu Ser Ala Ala Tyr 225 230 235 240 Phe Ala Asn Tyr Gly Lys Gly Gly Val Asn Val Gly Gly Lys Ser Phe 245 250 255 Ala Tyr Lys Ala Asp Asn Gln Gln Gln Tyr Ser Ala Gly Val Ala Leu 260 265 270 Leu Tyr Arg Asn Val Thr Leu Asn Val Asn Gly Ser Ile Thr Lys Gly 275 280 285 Lys Gln Leu Glu Lys Gln Lys Ser Gly Gln Ile Lys Ile Gln Ile Arg 290 295 300 Phe 305 <210> SEQ ID NO 1465 <211> LENGTH: 232 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1465 Met Leu Ile Asn Arg Asn Ile Val Ala Leu Phe Ala Leu Pro Phe Met 1 5 10 15 Ala Ser Ala Thr Ala Ser Glu Leu Ser Ile Gly Ala Gly Ala Ala Tyr 20 25 30 Asn Glu Ser Pro Tyr Arg Gly Tyr Asn Glu Asn Thr Lys Ala Ile Pro 35 40 45 Leu Ile Ser Tyr Glu Gly Asp Thr Phe Tyr Val Arg Gln Thr Thr Leu 50 55 60 Gly Phe Ile Leu Ser Gln Ser Glu Lys Asn Glu Leu Ser Leu Thr Ala 65 70 75 80 Ser Trp Met Pro Leu Glu Phe Asp Pro Thr Asp Asn Asp Asp Tyr Ala 85 90 95 Met Gln Gln Leu Asp Lys Arg Asp Ser Thr Ala Met Ala Gly Val Ala 100 105 110 Trp Tyr His His Glu Arg Trp Gly Thr Val Lys Ala Ser Ala Ala Ala 115 120 125 Asp Val Leu Asp Asn Ser Asn Gly Trp Val Gly Glu Leu Ser Val Phe 130 135 140 His Lys Met Gln Ile Gly Arg Leu Ser Leu Thr Pro Ala Leu Gly Val 145 150 155 160 Leu Tyr Tyr Asp Glu Asn Phe Ser Asp Tyr Tyr Tyr Gly Ile Ser Glu 165 170 175 Ser Glu Ser Arg Arg Ser Gly Leu Ala Ser Tyr Ser Ala Gln Asp Ala 180 185 190 Trp Val Pro Tyr Val Ser Leu Thr Ala Lys Tyr Pro Ile Gly Glu His 195 200 205 Val Val Leu Met Ala Ser Ala Gly Tyr Ser Glu Leu Pro Glu Glu Ile 210 215 220 Thr Asp Ser Pro Met Ile Asp Arg 225 230 <210> SEQ ID NO 1466 <400> SEQUENCE: 1466 000 <210> SEQ ID NO 1467 <400> SEQUENCE: 1467 000 <210> SEQ ID NO 1468 <400> SEQUENCE: 1468 000 <210> SEQ ID NO 1469 <400> SEQUENCE: 1469 000 <210> SEQ ID NO 1470 <400> SEQUENCE: 1470 000 <210> SEQ ID NO 1471 <400> SEQUENCE: 1471 000 <210> SEQ ID NO 1472 <400> SEQUENCE: 1472 000 <210> SEQ ID NO 1473 <400> SEQUENCE: 1473 000 <210> SEQ ID NO 1474 <400> SEQUENCE: 1474 000 <210> SEQ ID NO 1475 <400> SEQUENCE: 1475 000 <210> SEQ ID NO 1476 <400> SEQUENCE: 1476 000 <210> SEQ ID NO 1477 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1477 Gly Gly Gly Gly Ser 1 5 <210> SEQ ID NO 1478 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1478 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 <210> SEQ ID NO 1479 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1479 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 15 <210> SEQ ID NO 1480 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1480 Glu Ala Ala Ala Lys 1 5 <210> SEQ ID NO 1481 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1481 Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys 1 5 10 <210> SEQ ID NO 1482 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1482 Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys 1 5 10 15 <210> SEQ ID NO 1483 <211> LENGTH: 173 <212> TYPE: PRT <213> ORGANISM: Escherichia coli <400> SEQUENCE: 1483 Met Gln Leu Asn Lys Val Leu Lys Gly Leu Met Ile Ala Leu Pro Val 1 5 10 15 Met Ala Ile Ala Ala Cys Ser Ser Asn Lys Asn Ala Ser Asn Asp Gly 20 25 30 Ser Glu Gly Met Leu Gly Ala Gly Thr Gly Met Asp Ala Asn Gly Gly 35 40 45 Asn Gly Asn Met Ser Ser Glu Glu Gln Ala Arg Leu Gln Met Gln Gln 50 55 60 Leu Gln Gln Asn Asn Ile Val Tyr Phe Asp Leu Asp Lys Tyr Asp Ile 65 70 75 80 Arg Ser Asp Phe Ala Gln Met Leu Asp Ala His Ala Asn Phe Leu Arg 85 90 95 Ser Asn Pro Ser Tyr Lys Val Thr Val Glu Gly His Ala Asp Glu Arg 100 105 110 Gly Thr Pro Glu Tyr Asn Ile Ser Leu Gly Glu Arg Arg Ala Asn Ala 115 120 125 Val Lys Met Tyr Leu Gln Gly Lys Gly Val Ser Ala Asp Gln Ile Ser 130 135 140 Ile Val Ser Tyr Gly Lys Glu Lys Pro Ala Val Leu Gly His Asp Glu 145 150 155 160 Ala Ala Tyr Ala Lys Asn Arg Arg Ala Val Leu Val Tyr 165 170 <210> SEQ ID NO 1484 <211> LENGTH: 4307 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1484 tagcggagtg tatactggct tactatgttg gcactgatga gggtgtcagt gaagtgcttc 60 atgtggcagg agaaaaaagg ctgcaccggt gcgtcagcag aatatgtgat acaggatata 120 ttccgcttcc tcgctcactg actcgctacg ctcggtcgtt cgactgcggc gagcggaaat 180 ggcttacgaa cggggcggag atttcctgga agatgccagg aagatactta acagggaagt 240 gagagggccg cggcaaagcc gtttttccat aggctccgcc cccctgacaa gcatcacgaa 300 atctgacgct caaatcagtg gtggcgaaac ccgacaggac tataaagata ccaggcgttt 360 cccctggcgg ctccctcgtg cgctctcctg ttcctgcctt tcggtttacc ggtgtcattc 420 cgctgttatg gccgcgtttg tctcattcca cgcctgacac tcagttccgg gtaggcagtt 480 cgctccaagc tggactgtat gcacgaaccc cccgttcagt ccgaccgctg cgccttatcc 540 ggtaactatc gtcttgagtc caacccggaa agacatgcaa aagcaccact ggcagcagcc 600 actggtaatt gatttagagg agttagtctt gaagtcatgc gccggttaag gctaaactga 660 aaggacaagt tttggtgact gcgctcctcc aagccagtta cctcggttca aagagttggt 720 agctcagaga accttcgaaa aaccgccctg caaggcggtt ttttcgtttt cagagcaaga 780 gattacgcgc agaccaaaac gatctcaaga agatcatctt attaaggggt ctgacgctca 840 gtggaacggt gcaccctgca gggctagctg ataaagcgtt cgcgctgcat tcggcagttt 900 aagacccact ttcacattta agttgttttt ctaatccgca tatgatcaat tcaaggccga 960 ataagaaggc tggctctgca ccttggtgat caaataattc gatagcttgt cgtaataatg 1020 gcggcatact atcagtagta ggtgtttccc tttcttcttt agcgacttga tgctcttgat 1080 cttccaatac gcaacctaaa gtaaaatgcc ccacagcgct gagtgcatat aatgcattct 1140 ctagtgaaaa accttgttgg cataaaaagg ctaattgatt ttcgagagtt tcatactgtt 1200 tttctgtagg ccgtgtacct aaatgtactt ttgctccatc gcgatgactt agtaaagcac 1260 atctaaaact tttagcgtta ttacgtaaaa aatcttgcca gctttcccct tctaaagggc 1320 aaaagtgagt atggtgccta tctaacatct caatggctaa ggcgtcgagc aaagcccgct 1380 tattttttac atgccaatac aatgtaggct gctctacacc tagcttctgg gcgagtttac 1440 gggttgttaa accttcgatt ccgacctcat taagcagctc taatgcgctg ttaatcactt 1500 tacttttatc taatctagac atcattaatt cctaattttt gttgacactc tatcattgat 1560 agagttattt taccactccc tatcagtgat agagaaaagt gaaaggaggt aaattatgaa 1620 atatcttctt ccaacggctg ctgctggttt attgcttctt gccgcccagc ctgcgatggc 1680 tactagtgac tataaggatg acgacgacaa gagatctacg gcattgacgg aaggtgcaaa 1740 actgtttgag aaagagatcc cgtatatcac cgaactggaa ggcgacgtcg aaggtatgaa 1800 atttatcatt aaaggcgagg gtaccggtga cgcgaccacg ggtaccatta aagcgaaata 1860 catctgcact acgggcgacc tgccggtccc gtgggcaacc ctggtgagca ccctgagcta 1920 cggtgttcag tgtttcgcca agtacccgag ccacatcaag gatttcttta agagcgccat 1980 gccggaaggt tatacccaag agcgtaccat cagcttcgaa ggcgacggcg tgtacaagac 2040 gcgtgctatg gttacctacg aacgcggttc tatctacaat cgtgtcacgc tgactggtga 2100 gaactttaag aaagacggtc acattctgcg taagaacgtt gcattccaat gcccgccaag 2160 cattctgtat attctgcctg acaccgttaa caatggcatc cgcgttgagt tcaaccaggc 2220 gtacgatatt gaaggtgtga ccgaaaaact ggttaccaaa tgcagccaaa tgaatcgtcc 2280 gttggcgggc tccgcggcag tgcatatccc gcgttatcat cacattacct accacaccaa 2340 actgagcaaa gaccgcgacg agcgccgtga tcacatgtgt ctggtagagg tcgtgaaagc 2400 ggttgatctg gacacgtatc agggatccgg ccaccaccat catcaccact gcagtagcaa 2460 taaaaatgct tcgaatgacg gatcggaagg aatgttaggt gctggtactg gcatggacgc 2520 caacggtggc aacggaaata tgtctagcga agaacaagct cgtttacaaa tgcagcaatt 2580 acagcaaaac aacatagtct acttcgactt agacaagtac gacatccgta gcgattttgc 2640 acaaatgttg gatgcccatg ccaacttcct tcgttctaat ccaagctaca aagtcactgt 2700 tgagggccac gcggatgaga gaggcactcc tgaatataac atatccctgg gggagcgcag 2760 agcaaacgcc gtaaaaatgt acctgcaagg caagggcgtc tcggccgatc aaatctcgat 2820 cgtgagctat ggcaaagaga aaccggctgt attgggacat gacgaagctg cttacagcaa 2880 gaatcggcgg gccgtcttgg tctactaata agcatgctaa tcagccgtgg aattcgcaac 2940 gtaaaaaaac ccgccccggc gggttttttt ataccggtct caggaggaac gattggtaaa 3000 cccggtgaac gcatgagaaa gcccccggaa gatcaccttc cgggggcttt tttattgcgc 3060 ggaccaaaac gaaaaaagac gctcgaaagc gtctcttttc tggaatttgg taccgaggcg 3120 taatgctctg ccagtgttac aaccaattaa ccaattctga ttagaaaaac tcatcgagca 3180 tcaaatgaaa ctgcaattta ttcatatcag gattatcaat accatatttt tgaaaaagcc 3240 gtttctgtaa tgaaggagaa aactcaccga ggcagttcca taggatggca agatcctggt 3300 atcggtctgc gattccgact cgtccaacat caatacaacc tattaatttc ccctcgtcaa 3360 aaataaggtt atcaagtgag aaatcaccat gagtgacgac tgaatccggt gagaatggca 3420 aaagcttatg catttctttc cagacttgtt caacaggcca gccattacgc tcgtcatcaa 3480 aatcactcgc atcaaccaaa ccgttattca ttcgtgattg cgcctgagcg agacgaaata 3540 cgcgatcgct gttaaaagga caattacaaa caggaatcga atgcaaccgg cgcaggaaca 3600 ctgccagcgc atcaacaata ttttcacctg aatcaggata ttcttctaat acctggaatg 3660 ctgttttccc ggggatcgca gtggtgagta accatgcatc atcaggagta cggataaaat 3720 gcttgatggt cggaagaggc ataaattccg tcagccagtt tagtctgacc atctcatctg 3780 taacatcatt ggcaacgcta cctttgccat gtttcagaaa caactctggc gcatcgggct 3840 tcccatacaa tcgatagatt gtcgcacctg attgcccgac attatcgcga gcccatttat 3900 acccatataa atcagcatcc atgttggaat ttaatcgcgg cctcgagcaa gacgtttccc 3960 gttgaatatg gctcataaca ccccttgtat tactgtttat gtaagcagac agttttattg 4020 ttcatgatga tatattttta tcttgtgcaa tgtaacatca gagattttga gacacaacgt 4080 ggctttgttg aataaatcga acttttgctg agttgaagga tcagatcacg catcttcccg 4140 acaacgcaga ccgttccgtg gcaaagcaaa agttcaaaat caccaactgg tccacctaca 4200 acaaagctct catcaaccgt ggctccctca ctttctggct ggatgatggg gcgattcagg 4260 cctggtatga gtcagcaaca ccttcttcac gaggcagacc tcagcgc 4307 <210> SEQ ID NO 1485 <211> LENGTH: 3811 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1485 tagcggagtg tatactggct tactatgttg gcactgatga gggtgtcagt gaagtgcttc 60 atgtggcagg agaaaaaagg ctgcaccggt gcgtcagcag aatatgtgat acaggatata 120 ttccgcttcc tcgctcactg actcgctacg ctcggtcgtt cgactgcggc gagcggaaat 180 ggcttacgaa cggggcggag atttcctgga agatgccagg aagatactta acagggaagt 240 gagagggccg cggcaaagcc gtttttccat aggctccgcc cccctgacaa gcatcacgaa 300 atctgacgct caaatcagtg gtggcgaaac ccgacaggac tataaagata ccaggcgttt 360 cccctggcgg ctccctcgtg cgctctcctg ttcctgcctt tcggtttacc ggtgtcattc 420 cgctgttatg gccgcgtttg tctcattcca cgcctgacac tcagttccgg gtaggcagtt 480 cgctccaagc tggactgtat gcacgaaccc cccgttcagt ccgaccgctg cgccttatcc 540 ggtaactatc gtcttgagtc caacccggaa agacatgcaa aagcaccact ggcagcagcc 600 actggtaatt gatttagagg agttagtctt gaagtcatgc gccggttaag gctaaactga 660 aaggacaagt tttggtgact gcgctcctcc aagccagtta cctcggttca aagagttggt 720 agctcagaga accttcgaaa aaccgccctg caaggcggtt ttttcgtttt cagagcaaga 780 gattacgcgc agaccaaaac gatctcaaga agatcatctt attaaggggt ctgacgctca 840 gtggaacggt gcaccctgca gggctagctg ataaagcgtt cgcgctgcat tcggcagttt 900 aagacccact ttcacattta agttgttttt ctaatccgca tatgatcaat tcaaggccga 960 ataagaaggc tggctctgca ccttggtgat caaataattc gatagcttgt cgtaataatg 1020 gcggcatact atcagtagta ggtgtttccc tttcttcttt agcgacttga tgctcttgat 1080 cttccaatac gcaacctaaa gtaaaatgcc ccacagcgct gagtgcatat aatgcattct 1140 ctagtgaaaa accttgttgg cataaaaagg ctaattgatt ttcgagagtt tcatactgtt 1200 tttctgtagg ccgtgtacct aaatgtactt ttgctccatc gcgatgactt agtaaagcac 1260 atctaaaact tttagcgtta ttacgtaaaa aatcttgcca gctttcccct tctaaagggc 1320 aaaagtgagt atggtgccta tctaacatct caatggctaa ggcgtcgagc aaagcccgct 1380 tattttttac atgccaatac aatgtaggct gctctacacc tagcttctgg gcgagtttac 1440 gggttgttaa accttcgatt ccgacctcat taagcagctc taatgcgctg ttaatcactt 1500 tacttttatc taatctagac atcattaatt cctaattttt gttgacactc tatcattgat 1560 agagttattt taccactccc tatcagtgat agagaaaagt gaaaggaggt aaattatgac 1620 tagtgctttt gaccccaatc tggttgggcc tacgttacct ccaattccgc ctttcactct 1680 gcctacggac tataaggatg acgacgacaa gagatctacg gcattgacgg aaggtgcaaa 1740 actgtttgag aaagagatcc cgtatatcac cgaactggaa ggcgacgtcg aaggtatgaa 1800 atttatcatt aaaggcgagg gtaccggtga cgcgaccacg ggtaccatta aagcgaaata 1860 catctgcact acgggcgacc tgccggtccc gtgggcaacc ctggtgagca ccctgagcta 1920 cggtgttcag tgtttcgcca agtacccgag ccacatcaag gatttcttta agagcgccat 1980 gccggaaggt tatacccaag agcgtaccat cagcttcgaa ggcgacggcg tgtacaagac 2040 gcgtgctatg gttacctacg aacgcggttc tatctacaat cgtgtcacgc tgactggtga 2100 gaactttaag aaagacggtc acattctgcg taagaacgtt gcattccaat gcccgccaag 2160 cattctgtat attctgcctg acaccgttaa caatggcatc cgcgttgagt tcaaccaggc 2220 gtacgatatt gaaggtgtga ccgaaaaact ggttaccaaa tgcagccaaa tgaatcgtcc 2280 gttggcgggc tccgcggcag tgcatatccc gcgttatcat cacattacct accacaccaa 2340 actgagcaaa gaccgcgacg agcgccgtga tcacatgtgt ctggtagagg tcgtgaaagc 2400 ggttgatctg gacacgtatc agggatccgg ccaccaccat catcaccact aataagcatg 2460 ctaatcagcc gtggaattcg gtctcaggag gaacgattgg taaacccggt gaacgcatga 2520 gaaagccccc ggaagatcac cttccggggg cttttttatt gcgcggacca aaacgaaaaa 2580 agacgctcga aagcgtctct tttctggaat ttggtaccga ggcgtaatgc tctgccagtg 2640 ttacaaccaa ttaaccaatt ctgattagaa aaactcatcg agcatcaaat gaaactgcaa 2700 tttattcata tcaggattat caataccata tttttgaaaa agccgtttct gtaatgaagg 2760 agaaaactca ccgaggcagt tccataggat ggcaagatcc tggtatcggt ctgcgattcc 2820 gactcgtcca acatcaatac aacctattaa tttcccctcg tcaaaaataa ggttatcaag 2880 tgagaaatca ccatgagtga cgactgaatc cggtgagaat ggcaaaagct tatgcatttc 2940 tttccagact tgttcaacag gccagccatt acgctcgtca tcaaaatcac tcgcatcaac 3000 caaaccgtta ttcattcgtg attgcgcctg agcgagacga aatacgcgat cgctgttaaa 3060 aggacaatta caaacaggaa tcgaatgcaa ccggcgcagg aacactgcca gcgcatcaac 3120 aatattttca cctgaatcag gatattcttc taatacctgg aatgctgttt tcccggggat 3180 cgcagtggtg agtaaccatg catcatcagg agtacggata aaatgcttga tggtcggaag 3240 aggcataaat tccgtcagcc agtttagtct gaccatctca tctgtaacat cattggcaac 3300 gctacctttg ccatgtttca gaaacaactc tggcgcatcg ggcttcccat acaatcgata 3360 gattgtcgca cctgattgcc cgacattatc gcgagcccat ttatacccat ataaatcagc 3420 atccatgttg gaatttaatc gcggcctcga gcaagacgtt tcccgttgaa tatggctcat 3480 aacacccctt gtattactgt ttatgtaagc agacagtttt attgttcatg atgatatatt 3540 tttatcttgt gcaatgtaac atcagagatt ttgagacaca acgtggcttt gttgaataaa 3600 tcgaactttt gctgagttga aggatcagat cacgcatctt cccgacaacg cagaccgttc 3660 cgtggcaaag caaaagttca aaatcaccaa ctggtccacc tacaacaaag ctctcatcaa 3720 ccgtggctcc ctcactttct ggctggatga tggggcgatt caggcctggt atgagtcagc 3780 aacaccttct tcacgaggca gacctcagcg c 3811 <210> SEQ ID NO 1486 <211> LENGTH: 4195 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1486 tggcataaaa aggctaattg attttcgaga gtttcatact gtttttctgt aggccgtgta 60 cctaaatgta cttttgctcc atcgcgatga cttagtaaag cacatctaaa acttttagcg 120 ttattacgta aaaaatcttg ccagctttcc ccttctaaag ggcaaaagtg agtatggtgc 180 ctatctaaca tctcaatggc taaggcgtcg agcaaagccc gcttattttt tacatgccaa 240 tacaatgtag gctgctctac acctagcttc tgggcgagtt tacgggttgt taaaccttcg 300 attccgacct cattaagcag ctctaatgcg ctgttaatca ctttactttt atctaatcta 360 gacatcatta attcctaatt tttgttgaca ctctatcatt gatagagtta ttttaccact 420 ccctatcagt gatagagaaa agtgaaagga ggtaaattat gactagtaaa gcaacaaaac 480 ttgtgttagg cgcggttata cttggctcca ccctgcttgc aggttgctcg tctaacgcga 540 agatcgacca gggtatcaat ccttacgtcg ggtttgaaat gggatacgat tggttgggac 600 gtatgcctta taagggaagt gttgaaaacg gcgcttataa ggcgcaggga gtacagttaa 660 cggccaagct tgggtacccc ataacagacg atttagatat ttatacccgt ttaggaggaa 720 tggtttggag agccgacacg aagtctaatg tatatggtaa gaaccacgac acgggagtat 780 cccccgtctt tgcaggggga gtggaatatg ctatcacacc agagatcgct acccgtttgg 840 aatatcaatg gacgaataat ataggcgacg cccatacgat aggaacgcgg cccgacaacg 900 gcatccctgg ggtcgactat aaggatgacg acgacaagca attgacggca ttgacggaag 960 gtgcaaaact gtttgagaaa gagatcccgt atatcaccga actggaaggc gacgtcgaag 1020 gtatgaaatt tatcattaaa ggcgagggta ccggtgacgc gaccacgggt accattaaag 1080 cgaaatacat ctgcactacg ggcgacctgc cggtcccgtg ggcaaccctg gtgagcaccc 1140 tgagctacgg tgttcagtgt ttcgccaagt acccgagcca catcaaggat ttctttaaga 1200 gcgccatgcc ggaaggttat acccaagagc gtaccatcag cttcgaaggc gacggcgtgt 1260 acaagacgcg tgctatggtt acctacgaac gcggttctat ctacaatcgt gtcacgctga 1320 ctggtgagaa ctttaagaaa gacggtcaca ttctgcgtaa gaacgttgca ttccaatgcc 1380 cgccaagcat tctgtatatt ctgcctgaca ccgttaacaa tggcatccgc gttgagttca 1440 accaggcgta cgatattgaa ggtgtgaccg aaaaactggt taccaaatgc agccaaatga 1500 atcgtccgtt ggcgggctcc gcggcagtgc atatcccgcg ttatcatcac attacctacc 1560 acaccaaact gagcaaagac cgcgacgagc gccgtgatca catgtgtctg gtagaggtcg 1620 tgaaagcggt tgatctggac acgtatcagg gatccggcca ccaccatcat caccactaat 1680 aagcatgcta atcagccgtg gaattcggtc tcaggaggaa cgattggtaa acccggtgaa 1740 cgcatgagaa agcccccgga agatcacctt ccgggggctt ttttattgcg cggaccaaaa 1800 cgaaaaaaga cgctcgaaag cgtctctttt ctggaatttg gtaccgaggc gtaatgctct 1860 gccagtgtta caaccaatta accaattctg attagaaaaa ctcatcgagc atcaaatgaa 1920 actgcaattt attcatatca ggattatcaa taccatattt ttgaaaaagc cgtttctgta 1980 atgaaggaga aaactcaccg aggcagttcc ataggatggc aagatcctgg tatcggtctg 2040 cgattccgac tcgtccaaca tcaatacaac ctattaattt cccctcgtca aaaataaggt 2100 tatcaagtga gaaatcacca tgagtgacga ctgaatccgg tgagaatggc aaaagcttat 2160 gcatttcttt ccagacttgt tcaacaggcc agccattacg ctcgtcatca aaatcactcg 2220 catcaaccaa accgttattc attcgtgatt gcgcctgagc gagacgaaat acgcgatcgc 2280 tgttaaaagg acaattacaa acaggaatcg aatgcaaccg gcgcaggaac actgccagcg 2340 catcaacaat attttcacct gaatcaggat attcttctaa tacctggaat gctgttttcc 2400 cggggatcgc agtggtgagt aaccatgcat catcaggagt acggataaaa tgcttgatgg 2460 tcggaagagg cataaattcc gtcagccagt ttagtctgac catctcatct gtaacatcat 2520 tggcaacgct acctttgcca tgtttcagaa acaactctgg cgcatcgggc ttcccataca 2580 atcgatagat tgtcgcacct gattgcccga cattatcgcg agcccattta tacccatata 2640 aatcagcatc catgttggaa tttaatcgcg gcctcgagca agacgtttcc cgttgaatat 2700 ggctcataac accccttgta ttactgttta tgtaagcaga cagttttatt gttcatgatg 2760 atatattttt atcttgtgca atgtaacatc agagattttg agacacaacg tggctttgtt 2820 gaataaatcg aacttttgct gagttgaagg atcagatcac gcatcttccc gacaacgcag 2880 accgttccgt ggcaaagcaa aagttcaaaa tcaccaactg gtccacctac aacaaagctc 2940 tcatcaaccg tggctccctc actttctggc tggatgatgg ggcgattcag gcctggtatg 3000 agtcagcaac accttcttca cgaggcagac ctcagcgcta gcggagtgta tactggctta 3060 ctatgttggc actgatgagg gtgtcagtga agtgcttcat gtggcaggag aaaaaaggct 3120 gcaccggtgc gtcagcagaa tatgtgatac aggatatatt ccgcttcctc gctcactgac 3180 tcgctacgct cggtcgttcg actgcggcga gcggaaatgg cttacgaacg gggcggagat 3240 ttcctggaag atgccaggaa gatacttaac agggaagtga gagggccgcg gcaaagccgt 3300 ttttccatag gctccgcccc cctgacaagc atcacgaaat ctgacgctca aatcagtggt 3360 ggcgaaaccc gacaggacta taaagatacc aggcgtttcc cctggcggct ccctcgtgcg 3420 ctctcctgtt cctgcctttc ggtttaccgg tgtcattccg ctgttatggc cgcgtttgtc 3480 tcattccacg cctgacactc agttccgggt aggcagttcg ctccaagctg gactgtatgc 3540 acgaaccccc cgttcagtcc gaccgctgcg ccttatccgg taactatcgt cttgagtcca 3600 acccggaaag acatgcaaaa gcaccactgg cagcagccac tggtaattga tttagaggag 3660 ttagtcttga agtcatgcgc cggttaaggc taaactgaaa ggacaagttt tggtgactgc 3720 gctcctccaa gccagttacc tcggttcaaa gagttggtag ctcagagaac cttcgaaaaa 3780 ccgccctgca aggcggtttt ttcgttttca gagcaagaga ttacgcgcag accaaaacga 3840 tctcaagaag atcatcttat taaggggtct gacgctcagt ggaacggtgc accctgcagg 3900 gctagctgat aaagcgttcg cgctgcattc ggcagtttaa gacccacttt cacatttaag 3960 ttgtttttct aatccgcata tgatcaattc aaggccgaat aagaaggctg gctctgcacc 4020 ttggtgatca aataattcga tagcttgtcg taataatggc ggcatactat cagtagtagg 4080 tgtttccctt tcttctttag cgacttgatg ctcttgatct tccaatacgc aacctaaagt 4140 aaaatgcccc acagcgctga gtgcatataa tgcattctct agtgaaaaac cttgt 4195 <210> SEQ ID NO 1487 <211> LENGTH: 4744 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1487 aacgaaaaaa gacgctcgaa agcgtctctt ttctggaatt tggtaccgag gcgtaatgct 60 ctgccagtgt tacaaccaat taaccaattc tgattagaaa aactcatcga gcatcaaatg 120 aaactgcaat ttattcatat caggattatc aataccatat ttttgaaaaa gccgtttctg 180 taatgaagga gaaaactcac cgaggcagtt ccataggatg gcaagatcct ggtatcggtc 240 tgcgattccg actcgtccaa catcaataca acctattaat ttcccctcgt caaaaataag 300 gttatcaagt gagaaatcac catgagtgac gactgaatcc ggtgagaatg gcaaaagctt 360 atgcatttct ttccagactt gttcaacagg ccagccatta cgctcgtcat caaaatcact 420 cgcatcaacc aaaccgttat tcattcgtga ttgcgcctga gcgagacgaa atacgcgatc 480 gctgttaaaa ggacaattac aaacaggaat cgaatgcaac cggcgcagga acactgccag 540 cgcatcaaca atattttcac ctgaatcagg atattcttct aatacctgga atgctgtttt 600 cccggggatc gcagtggtga gtaaccatgc atcatcagga gtacggataa aatgcttgat 660 ggtcggaaga ggcataaatt ccgtcagcca gtttagtctg accatctcat ctgtaacatc 720 attggcaacg ctacctttgc catgtttcag aaacaactct ggcgcatcgg gcttcccata 780 caatcgatag attgtcgcac ctgattgccc gacattatcg cgagcccatt tatacccata 840 taaatcagca tccatgttgg aatttaatcg cggcctcgag caagacgttt cccgttgaat 900 atggctcata acaccccttg tattactgtt tatgtaagca gacagtttta ttgttcatga 960 tgatatattt ttatcttgtg caatgtaaca tcagagattt tgagacacaa cgtggctttg 1020 ttgaataaat cgaacttttg ctgagttgaa ggatcagatc acgcatcttc ccgacaacgc 1080 agaccgttcc gtggcaaagc aaaagttcaa aatcaccaac tggtccacct acaacaaagc 1140 tctcatcaac cgtggctccc tcactttctg gctggatgat ggggcgattc aggcctggta 1200 tgagtcagca acaccttctt cacgaggcag acctcagcgc tagcggagtg tatactggct 1260 tactatgttg gcactgatga gggtgtcagt gaagtgcttc atgtggcagg agaaaaaagg 1320 ctgcaccggt gcgtcagcag aatatgtgat acaggatata ttccgcttcc tcgctcactg 1380 actcgctacg ctcggtcgtt cgactgcggc gagcggaaat ggcttacgaa cggggcggag 1440 atttcctgga agatgccagg aagatactta acagggaagt gagagggccg cggcaaagcc 1500 gtttttccat aggctccgcc cccctgacaa gcatcacgaa atctgacgct caaatcagtg 1560 gtggcgaaac ccgacaggac tataaagata ccaggcgttt cccctggcgg ctccctcgtg 1620 cgctctcctg ttcctgcctt tcggtttacc ggtgtcattc cgctgttatg gccgcgtttg 1680 tctcattcca cgcctgacac tcagttccgg gtaggcagtt cgctccaagc tggactgtat 1740 gcacgaaccc cccgttcagt ccgaccgctg cgccttatcc ggtaactatc gtcttgagtc 1800 caacccggaa agacatgcaa aagcaccact ggcagcagcc actggtaatt gatttagagg 1860 agttagtctt gaagtcatgc gccggttaag gctaaactga aaggacaagt tttggtgact 1920 gcgctcctcc aagccagtta cctcggttca aagagttggt agctcagaga accttcgaaa 1980 aaccgccctg caaggcggtt ttttcgtttt cagagcaaga gattacgcgc agaccaaaac 2040 gatctcaaga agatcatctt attaaggggt ctgacgctca gtggaacggt gcaccctgca 2100 gggctagctg ataaagcgtt cgcgctgcat tcggcagttt aagacccact ttcacattta 2160 agttgttttt ctaatccgca tatgatcaat tcaaggccga ataagaaggc tggctctgca 2220 ccttggtgat caaataattc gatagcttgt cgtaataatg gcggcatact atcagtagta 2280 ggtgtttccc tttcttcttt agcgacttga tgctcttgat cttccaatac gcaacctaaa 2340 gtaaaatgcc ccacagcgct gagtgcatat aatgcattct ctagtgaaaa accttgttgg 2400 cataaaaagg ctaattgatt ttcgagagtt tcatactgtt tttctgtagg ccgtgtacct 2460 aaatgtactt ttgctccatc gcgatgactt agtaaagcac atctaaaact tttagcgtta 2520 ttacgtaaaa aatcttgcca gctttcccct tctaaagggc aaaagtgagt atggtgccta 2580 tctaacatct caatggctaa ggcgtcgagc aaagcccgct tattttttac atgccaatac 2640 aatgtaggct gctctacacc tagcttctgg gcgagtttac gggttgttaa accttcgatt 2700 ccgacctcat taagcagctc taatgcgctg ttaatcactt tacttttatc taatctagac 2760 atcattaatt cctaattttt gttgacactc tatcattgat agagttattt taccactccc 2820 tatcagtgat agagaaaagt gaaaggaggt aaattatgac tagtaaggca aaacgcttca 2880 agattaacgc tatcagttta tccatctttt tagcgtatgc gttgactccg tactcagagg 2940 cagtcgacta taaggatgac gacgacaagc aattgacggc attgacggaa ggtgcaaaac 3000 tgtttgagaa agagatcccg tatatcaccg aactggaagg cgacgtcgaa ggtatgaaat 3060 ttatcattaa aggcgagggt accggtgacg cgaccacggg taccattaaa gcgaaataca 3120 tctgcactac gggcgacctg ccggtcccgt gggcaaccct ggtgagcacc ctgagctacg 3180 gtgttcagtg tttcgccaag tacccgagcc acatcaagga tttctttaag agcgccatgc 3240 cggaaggtta tacccaagag cgtaccatca gcttcgaagg cgacggcgtg tacaagacgc 3300 gtgctatggt tacctacgaa cgcggttcta tctacaatcg tgtcacgctg actggtgaga 3360 actttaagaa agacggtcac attctgcgta agaacgttgc attccaatgc ccgccaagca 3420 ttctgtatat tctgcctgac accgttaaca atggcatccg cgttgagttc aaccaggcgt 3480 acgatattga aggtgtgacc gaaaaactgg ttaccaaatg cagccaaatg aatcgtccgt 3540 tggcgggctc cgcggcagtg catatcccgc gttatcatca cattacctac cacaccaaac 3600 tgagcaaaga ccgcgacgag cgccgtgatc acatgtgtct ggtagaggtc gtgaaagcgg 3660 ttgatctgga cacgtatcag ggatccggcc accaccatca tcaccacccg cgtgctgcac 3720 aaccgcgtac acaagctgca gcccaggccg acgcagtatc cacgaacaca aattcagcgt 3780 tgagtgatgc tatggcttca actcaatcaa ttcttttgga caccggcgca tatttaactc 3840 gccatatcgc ccaaaagtct cgtgcggatg cagaaaaaaa tagcgtgtgg atgtcgaata 3900 ctgggtatgg gcgcgactac gcctctgcgc agtaccgccg tttcagcagc aaacgcaccc 3960 agactcaaat cgggatcgat cgtagtctta gtgagaatat gcagattggc ggagttctga 4020 cttattccga ctctcaacat acgttcgacc aggcaggggg caagaatacg tttgtacagg 4080 ccaatcttta cggaaagtac tacttgaatg atgcctggta tgtcgctggg gacattggcg 4140 cagggagctt gcgttcccgc cttcaaacgc aacaaaaggc gaatttcaat cgcaccagca 4200 ttcagactgg ccttacactt gggaatacac ttaagattaa tcaatttgag attgtgccca 4260 gtgctgggat tcgttatagt cgtttatcca gcgcagacta taagttaggc gacgactctg 4320 tgaaagttag ctcaatggcc gtgaagacgt tgacggctgg tttggatttc gcctatcgct 4380 ttaaagttgg aaatctgacc gtgaagccgc tgctttcggc cgcttatttt gcaaactacg 4440 gcaagggcgg cgttaatgtc ggtggtaaga gtttcgccta taaagctgac aatcagcagc 4500 aatattcggc cggcgtcgcg ttgttgtatc gcaacgtgac tttaaatgta aacggctcca 4560 tcacaaaggg caagcagttg gagaagcaaa agtcaggcca aatcaagatt caaatccgtt 4620 tctaataagc atgctaatca gccgtggaat tcggtctcag gaggaacgat tggtaaaccc 4680 ggtgaacgca tgagaaagcc cccggaagat caccttccgg gggctttttt attgcgcgga 4740 ccaa 4744 <210> SEQ ID NO 1488 <211> LENGTH: 56 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1488 gttgacactc tatcattgat agagttattt taccactccc tatcagtgat agagaa 56 <210> SEQ ID NO 1489 <211> LENGTH: 456 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1489 tgcagtagca ataaaaatgc ttcgaatgac ggatcggaag gaatgttagg tgctggtact 60 ggcatggacg ccaacggtgg caacggaaat atgtctagcg aagaacaagc tcgtttacaa 120 atgcagcaat tacagcaaaa caacatagtc tacttcgact tagacaagta cgacatccgt 180 agcgattttg cacaaatgtt ggatgcccat gccaacttcc ttcgttctaa tccaagctac 240 aaagtcactg ttgagggcca cgcggatgag agaggcactc ctgaatataa catatccctg 300 ggggagcgca gagcaaacgc cgtaaaaatg tacctgcaag gcaagggcgt ctcggccgat 360 caaatctcga tcgtgagcta tggcaaagag aaaccggctg tattgggaca tgacgaagct 420 gcttacagca agaatcggcg ggccgtcttg gtctac 456 <210> SEQ ID NO 1490 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1490 gcttttgacc ccaatctggt tgggcctacg ttacctccaa ttccgccttt cactctgcct 60 acg 63 <210> SEQ ID NO 1491 <211> LENGTH: 442 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1491 atgactagtt aaagcaacaa aacttgtgtt aggcgcggtt atacttggct ccaccctgct 60 tgcaggttgc tcgtctaacg cgaagatcga ccagggtatc aatccttacg tcgggtttga 120 aatgggatac gattggttgg gacgtatgcc ttataaggga agtgttgaaa acggcgctta 180 taaggcgcag ggagtacagt taacggccaa gcttgggtac cccataacag acgatttaga 240 tatttatacc cgtttaggag gaatggtttg gagagccgac acgaagtcta atgtatatgg 300 taagaaccac gacacgggag tatcccccgt ctttgcaggg ggagtggaat atgctatcac 360 accagagatc gctacccgtt tggaatatca atggacgaat aatataggcg acgcccatac 420 gataggaacg cggcccgaca ac 442 <210> SEQ ID NO 1492 <211> LENGTH: 603 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1492 atgacaatga ctcgtttgaa aatttccaaa accctgctgg ccgtaatgct tacgtccgca 60 gtcgccactg gttccgcata cgcagagaat aatgcgcaga caactaacga gtcagcaggg 120 caaaaagtag actccagtat gaataaggtg ggcaatttta tggacgactc agctatcacc 180 gctaaggtga aagcggcgct ggtggaccac gacaacatca agtccacgga catctcagtt 240 aaaacggacc aaaaggtagt aaccttaagc gggttcgtag aaagccaggc gcaagcagag 300 gaagcggtaa aagtcgctaa aggcgtagaa ggggtcactt cggtgtcaga caagttgcat 360 gtgcgtgacg caaaggaagg atcagtaaag ggttatgccg gagatacggc aacgacctct 420 gagatcaaag cgaaattact ggcagacgac attgttccct cgcgtcatgt taaagtcgaa 480 acgactgatg gcgtagtcca gctttcgggt acagttgact cccaagcaca aagtgatcgc 540 gcggaatcta ttgcaaaggc ggtggacgga gtgaaatccg tcaaaaacga tcttaaaacg 600 aaa 603 <210> SEQ ID NO 1493 <211> LENGTH: 1820 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1493 atggttttcc aacccatcag cgaatttttg ctgattcgta acgctgggat gtccatgtat 60 tttaacaaga tcatttcttt taacatcatt tcacgtatcg ttatttgcat ttttcttatc 120 tgtggtatgt tcatggccgg tgcatctgaa aagtatgatg caaacgcacc ccaacaggtg 180 cagccatact cggtttcatc atcagcgttc gagaatctgc accccaataa cgagatggag 240 tcgagtatca acccttttag tgcttcggac accgagcgta atgcagctat catcgatcgt 300 gctaacaagg aacaagaaac ggaagcagtc aacaaaatga tctccactgg cgctcgttta 360 gctgccagcg gtcgcgcgtc cgatgtggcg cacagtatgg taggggatgc ggtcaaccag 420 gagattaaac aatggctgaa tcgcttcggc actgctcaag tgaatttaaa ttttgacaag 480 aacttctcgt taaaggagtc ttcgcttgac tggttggccc catggtacga ttcggcgtca 540 ttccttttct tttctcagtt gggcatccgt aacaaggaca gtcgtaatac acttaacctt 600 ggtgttggca ttcgcacatt agaaaatggt tggttgtatg gcctgaacac cttttacgac 660 aatgacttaa cgggacacaa tcaccgtatc gggctgggcg ccgaggcgtg gactgactac 720 ttgcagttag ccgcgaatgg gtacttccgt cttaatggtt ggcactcttc ccgtgacttc 780 agcgactaca aagaacgccc tgctaccggg ggagatttgc gtgcgaatgc gtacctgccc 840 gctcttccgc aacttggcgg gaagttaatg tatgagcagt atactgggga acgcgtggct 900 ctgttcggaa aggacaacct gcagcgcaac ccatacgctg tcactgcggg tatcaactat 960 acgccagttc cgttgctgac ggtcggcgtg gatcaacgta tggggaagtc gagtaaacat 1020 gaaacgcaat ggaatttaca aatgaactat cgcttagggg agagtttcca aagtcagctt 1080 agcccttcgg cggtcgcagg gactcgtttg cttgctgagt cccgctacaa cctggttgat 1140 cgcaataaca atatcgtact ggaataccag aaacaacaag tggttaagct gacgttgagc 1200 cctgcgacca tcagtggatt gcccggacaa gtttaccagg taaatgccca ggtccagggg 1260 gcctctgcgg ttcgcgaaat tgtctggtca gacgcagaat taatcgctgc aggaggcacc 1320 ttaacgccac tttccactac acaattcaat ttagtccttc ccccatacaa acgtaccgcc 1380 caggtatcgc gcgtaactga tgacttaact gctaattttt attcactgtc ggcgttagca 1440 gttgaccatc aaggcaaccg tagtaattcc ttcacattat ctgtaacggt gcagcagccg 1500 caactgacgc ttaccgcagc ggtcattggt gatggggccc cagctaatgg gaaaaccgca 1560 atcactgtcg agttcacagt tgcagatttt gaaggcaagc cgctggcggg tcaggaggtt 1620 gtgattacga ctaataacgg tgctcttcct aataagatta ctgaaaagac tgacgctaac 1680 ggcgttgccc gcattgccct tacgaacaca accgatgggg tcacggtagt taccgcagag 1740 gtcgaggggc aacgccaatc cgttgacacg cacttcgtta agggtactat cgcggccgat 1800 aaaagcacgc tggccgcggt 1820 <210> SEQ ID NO 1494 <211> LENGTH: 1977 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1494 atgattacgc atggctgtta tacccgtacg cgtcataaac acaagttgaa gaaaactctg 60 atcatgttat ccgctggact tggacttttt ttttacgtga atcagaactc tttcgctaat 120 ggggaaaatt attttaaact gggatcagac agcaaattac ttacgcatga ctcataccag 180 aatcgtctgt tttatacgct gaaaactggt gaaaccgttg cagatttaag taaaagtcag 240 gacattaacc tgtcaactat ttggtcactt aataaacact tatattcgag cgaatcggaa 300 atgatgaaag ctgcaccggg gcaacaaatc atcttgcccc tgaagaaatt gccctttgaa 360 tactccgctt tgcccttgct gggctcggct cctctggtag ccgccggagg cgttgccggt 420 cacactaata agctgacaaa aatgtcaccc gacgtgacga agagcaacat gacggatgat 480 aaggctttaa attacgcagc tcagcaagcg gcctcgttgg gaagtcagtt acagagtcgt 540 tcgttaaatg gtgattatgc taaggatacc gcattgggta ttgccggcaa ccaagcgtcg 600 agccaacttc aggcatggtt gcaacattac ggcactgctg aagtaaatct gcaatcaggt 660 aataattttg acggtagttc cctggatttc cttttacctt tttacgattc agaaaagatg 720 ttggctttcg gacaggtggg ggcgcgttac atcgattcac gttttaccgc taacttgggg 780 gccggtcaac gcttcttctt acctgccaat atgttgggct ataatgtatt tatcgaccag 840 gacttcagtg gtgacaatac acgtctggga attggtggag agtattggcg cgattacttt 900 aagtcatctg taaatggcta ttttcgcatg agcggttggc atgaaagtta caacaagaaa 960 gactacgatg agcgccccgc gaacgggttt gacatccgtt ttaatggtta tttgccatct 1020 tatcccgcct tgggagctaa attaatctac gagcaatact atggagataa cgtagctttg 1080 tttaatagcg acaagttaca gtctaatcca ggagcggcta cagtgggagt taattatacc 1140 ccaatcccac tggtcacaat gggaatcgat tatcgccacg ggactggtaa tgaaaacgat 1200 ttattatact ccatgcagtt tcgttatcag ttcgataaga gttggtcgca gcagattgag 1260 cctcaatatg ttaacgaatt acgtaccttg tccggcagtc gctacgatct ggtacaacgc 1320 aataacaata tcatccttga gtataagaaa caggacattc tgtctttgaa cattccacat 1380 gatattaatg gtaccgagca ctcaacacaa aaaattcagc tgattgtgaa atcaaagtat 1440 ggactggacc gtatcgtgtg ggatgatagc gctctgcgca gtcagggtgg acagatccag 1500 cactcgggta gccagtctgc ccaagactac caggctatcc tgccagcgta tgtccaaggg 1560 ggaagtaaca tctacaaagt tacagctcgc gcctatgacc gcaacggtaa ttctagtaat 1620 aatgtgcagt tgacaattac ggtgctgtcc aatgggcagg tcgtcgatca ggtaggtgtg 1680 acggatttta cagccgataa aacctctgcg aaggcagata acgcggatac catcacatac 1740 actgccactg taaaaaaaaa cggtgtcgcg caggcaaacg ttcctgttag cttcaacatc 1800 gtgtcgggta cagccaccct tggggccaac tcggcaaaga ctgacgcgaa tggcaaggct 1860 acagtcacgt tgaaatcctc gacaccagga caggtcgttg tgtctgccaa gacagcagag 1920 atgacctccg cccttaatgc atctgctgtt atcttcttcg atcaaacgaa ggcatct 1977 <210> SEQ ID NO 1495 <211> LENGTH: 705 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1495 tcggcattga cggaaggtgc aaaactgttt gagaaagaga tcccgtatat caccgaactg 60 gaaggcgacg tcgaaggtat gaaatttatc attaaaggcg agggtaccgg tgacgcgacc 120 acgggtacca ttaaagcgaa atacatctgc actacgggcg acctgccggt cccgtgggca 180 accctggtga gcaccctgag ctacggtgtt cagtgtttcg ccaagtaccc gagccacatc 240 aaggatttct ttaagagcgc catgccggaa ggttataccc aagagcgtac catcagcttc 300 gaaggcgacg gcgtgtacaa gacgcgtgct atggttacct acgaacgcgg ttctatctac 360 aatcgtgtca cgctgactgg tgagaacttt aagaaagacg gtcacattct gcgtaagaac 420 gttgcattcc aatgcccgcc aagcattctg tatattctgc ctgacaccgt taacaatggc 480 atccgcgttg agttcaacca ggcgtacgat attgaaggtg tgaccgaaaa actggttacc 540 aaatgcagcc aaatgaatcg tccgttggcg ggctccgcgg cagtgcatat cccgcgttat 600 catcacatta cctaccacac caaactgagc aaagaccgcg acgagcgccg tgatcacatg 660 tgtctggtag aggtcgtgaa agcggttgat ctggacacgt atcag 705 <210> SEQ ID NO 1496 <211> LENGTH: 705 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1496 acggcattga cggaaggtgc aaaactgttt gagaaagaga tcccgtatat caccgaactg 60 gaaggcgacg tcgaaggtat gaaatttatc attaaaggcg agggtaccgg tgacgcgacc 120 acgggtacca ttaaagcgaa atacatctgc actacgggcg acctgccggt cccgtgggca 180 accctggtga gcaccctgag ctacggtgtt cagtgtttcg ccaagtaccc gagccacatc 240 aaggatttct ttaagagcgc catgccggaa ggttataccc aagagcgtac catcagcttc 300 gaaggcgacg gcgtgtacaa gacgcgtgct atggttacct acgaacgcgg ttctatctac 360 aatcgtgtca cgctgactgg tgagaacttt aagaaagacg gtcacattct gcgtaagaac 420 gttgcattcc aatgcccgcc aagcattctg tatattctgc ctgacaccgt taacaatggc 480 atccgcgttg agttcaacca ggcgtacgat attgaaggtg tgaccgaaaa actggttacc 540 aaatgcagcc aaatgaatcg tccgttggcg ggctccgcgg cagtgcatat cccgcgttat 600 catcacatta cctaccacac caaactgagc aaagaccgcg acgagcgccg tgatcacatg 660 tgtctggtag aggtcgtgaa agcggttgat ctggacacgt atcag 705 <210> SEQ ID NO 1497 <211> LENGTH: 152 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1497 Cys Ser Ser Asn Lys Asn Ala Ser Asn Asp Gly Ser Glu Gly Met Leu 1 5 10 15 Gly Ala Gly Thr Gly Met Asp Ala Asn Gly Gly Asn Gly Asn Met Ser 20 25 30 Ser Glu Glu Gln Ala Arg Leu Gln Met Gln Gln Leu Gln Gln Asn Asn 35 40 45 Ile Val Tyr Phe Asp Leu Asp Lys Tyr Asp Ile Arg Ser Asp Phe Ala 50 55 60 Gln Met Leu Asp Ala His Ala Asn Phe Leu Arg Ser Asn Pro Ser Tyr 65 70 75 80 Lys Val Thr Val Glu Gly His Ala Asp Glu Arg Gly Thr Pro Glu Tyr 85 90 95 Asn Ile Ser Leu Gly Glu Arg Arg Ala Asn Ala Val Lys Met Tyr Leu 100 105 110 Gln Gly Lys Gly Val Ser Ala Asp Gln Ile Ser Ile Val Ser Tyr Gly 115 120 125 Lys Glu Lys Pro Ala Val Leu Gly His Asp Glu Ala Ala Tyr Ser Lys 130 135 140 Asn Arg Arg Ala Val Leu Val Tyr 145 150 <210> SEQ ID NO 1498 <211> LENGTH: 24 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1498 Met Thr Ser Ala Phe Asp Pro Asn Leu Val Gly Pro Thr Leu Pro Pro 1 5 10 15 Ile Pro Pro Phe Thr Leu Pro Thr 20 <210> SEQ ID NO 1499 <211> LENGTH: 147 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1499 Met Thr Ser Lys Ala Thr Lys Leu Val Leu Gly Ala Val Ile Leu Gly 1 5 10 15 Ser Thr Leu Leu Ala Gly Cys Ser Ser Asn Ala Lys Ile Asp Gln Gly 20 25 30 Ile Asn Pro Tyr Val Gly Phe Glu Met Gly Tyr Asp Trp Leu Gly Arg 35 40 45 Met Pro Tyr Lys Gly Ser Val Glu Asn Gly Ala Tyr Lys Ala Gln Gly 50 55 60 Val Gln Leu Thr Ala Lys Leu Gly Tyr Pro Ile Thr Asp Asp Leu Asp 65 70 75 80 Ile Tyr Thr Arg Leu Gly Gly Met Val Trp Arg Ala Asp Thr Lys Ser 85 90 95 Asn Val Tyr Gly Lys Asn His Asp Thr Gly Val Ser Pro Val Phe Ala 100 105 110 Gly Gly Val Glu Tyr Ala Ile Thr Pro Glu Ile Ala Thr Arg Leu Glu 115 120 125 Tyr Gln Trp Thr Asn Asn Ile Gly Asp Ala His Thr Ile Gly Thr Arg 130 135 140 Pro Asp Asn 145 <210> SEQ ID NO 1500 <211> LENGTH: 201 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1500 Met Thr Met Thr Arg Leu Lys Ile Ser Lys Thr Leu Leu Ala Val Met 1 5 10 15 Leu Thr Ser Ala Val Ala Thr Gly Ser Ala Tyr Ala Glu Asn Asn Ala 20 25 30 Gln Thr Thr Asn Glu Ser Ala Gly Gln Lys Val Asp Ser Ser Met Asn 35 40 45 Lys Val Gly Asn Phe Met Asp Asp Ser Ala Ile Thr Ala Lys Val Lys 50 55 60 Ala Ala Leu Val Asp His Asp Asn Ile Lys Ser Thr Asp Ile Ser Val 65 70 75 80 Lys Thr Asp Gln Lys Val Val Thr Leu Ser Gly Phe Val Glu Ser Gln 85 90 95 Ala Gln Ala Glu Glu Ala Val Lys Val Ala Lys Gly Val Glu Gly Val 100 105 110 Thr Ser Val Ser Asp Lys Leu His Val Arg Asp Ala Lys Glu Gly Ser 115 120 125 Val Lys Gly Tyr Ala Gly Asp Thr Ala Thr Thr Ser Glu Ile Lys Ala 130 135 140 Lys Leu Leu Ala Asp Asp Ile Val Pro Ser Arg His Val Lys Val Glu 145 150 155 160 Thr Thr Asp Gly Val Val Gln Leu Ser Gly Thr Val Asp Ser Gln Ala 165 170 175 Gln Ser Asp Arg Ala Glu Ser Ile Ala Lys Ala Val Asp Gly Val Lys 180 185 190 Ser Val Lys Asn Asp Leu Lys Thr Lys 195 200 <210> SEQ ID NO 1501 <211> LENGTH: 659 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1501 Met Ile Thr His Gly Cys Tyr Thr Arg Thr Arg His Lys His Lys Leu 1 5 10 15 Lys Lys Thr Leu Ile Met Leu Ser Ala Gly Leu Gly Leu Phe Phe Tyr 20 25 30 Val Asn Gln Asn Ser Phe Ala Asn Gly Glu Asn Tyr Phe Lys Leu Gly 35 40 45 Ser Asp Ser Lys Leu Leu Thr His Asp Ser Tyr Gln Asn Arg Leu Phe 50 55 60 Tyr Thr Leu Lys Thr Gly Glu Thr Val Ala Asp Leu Ser Lys Ser Gln 65 70 75 80 Asp Ile Asn Leu Ser Thr Ile Trp Ser Leu Asn Lys His Leu Tyr Ser 85 90 95 Ser Glu Ser Glu Met Met Lys Ala Ala Pro Gly Gln Gln Ile Ile Leu 100 105 110 Pro Leu Lys Lys Leu Pro Phe Glu Tyr Ser Ala Leu Pro Leu Leu Gly 115 120 125 Ser Ala Pro Leu Val Ala Ala Gly Gly Val Ala Gly His Thr Asn Lys 130 135 140 Leu Thr Lys Met Ser Pro Asp Val Thr Lys Ser Asn Met Thr Asp Asp 145 150 155 160 Lys Ala Leu Asn Tyr Ala Ala Gln Gln Ala Ala Ser Leu Gly Ser Gln 165 170 175 Leu Gln Ser Arg Ser Leu Asn Gly Asp Tyr Ala Lys Asp Thr Ala Leu 180 185 190 Gly Ile Ala Gly Asn Gln Ala Ser Ser Gln Leu Gln Ala Trp Leu Gln 195 200 205 His Tyr Gly Thr Ala Glu Val Asn Leu Gln Ser Gly Asn Asn Phe Asp 210 215 220 Gly Ser Ser Leu Asp Phe Leu Leu Pro Phe Tyr Asp Ser Glu Lys Met 225 230 235 240 Leu Ala Phe Gly Gln Val Gly Ala Arg Tyr Ile Asp Ser Arg Phe Thr 245 250 255 Ala Asn Leu Gly Ala Gly Gln Arg Phe Phe Leu Pro Ala Asn Met Leu 260 265 270 Gly Tyr Asn Val Phe Ile Asp Gln Asp Phe Ser Gly Asp Asn Thr Arg 275 280 285 Leu Gly Ile Gly Gly Glu Tyr Trp Arg Asp Tyr Phe Lys Ser Ser Val 290 295 300 Asn Gly Tyr Phe Arg Met Ser Gly Trp His Glu Ser Tyr Asn Lys Lys 305 310 315 320 Asp Tyr Asp Glu Arg Pro Ala Asn Gly Phe Asp Ile Arg Phe Asn Gly 325 330 335 Tyr Leu Pro Ser Tyr Pro Ala Leu Gly Ala Lys Leu Ile Tyr Glu Gln 340 345 350 Tyr Tyr Gly Asp Asn Val Ala Leu Phe Asn Ser Asp Lys Leu Gln Ser 355 360 365 Asn Pro Gly Ala Ala Thr Val Gly Val Asn Tyr Thr Pro Ile Pro Leu 370 375 380 Val Thr Met Gly Ile Asp Tyr Arg His Gly Thr Gly Asn Glu Asn Asp 385 390 395 400 Leu Leu Tyr Ser Met Gln Phe Arg Tyr Gln Phe Asp Lys Ser Trp Ser 405 410 415 Gln Gln Ile Glu Pro Gln Tyr Val Asn Glu Leu Arg Thr Leu Ser Gly 420 425 430 Ser Arg Tyr Asp Leu Val Gln Arg Asn Asn Asn Ile Ile Leu Glu Tyr 435 440 445 Lys Lys Gln Asp Ile Leu Ser Leu Asn Ile Pro His Asp Ile Asn Gly 450 455 460 Thr Glu His Ser Thr Gln Lys Ile Gln Leu Ile Val Lys Ser Lys Tyr 465 470 475 480 Gly Leu Asp Arg Ile Val Trp Asp Asp Ser Ala Leu Arg Ser Gln Gly 485 490 495 Gly Gln Ile Gln His Ser Gly Ser Gln Ser Ala Gln Asp Tyr Gln Ala 500 505 510 Ile Leu Pro Ala Tyr Val Gln Gly Gly Ser Asn Ile Tyr Lys Val Thr 515 520 525 Ala Arg Ala Tyr Asp Arg Asn Gly Asn Ser Ser Asn Asn Val Gln Leu 530 535 540 Thr Ile Thr Val Leu Ser Asn Gly Gln Val Val Asp Gln Val Gly Val 545 550 555 560 Thr Asp Phe Thr Ala Asp Lys Thr Ser Ala Lys Ala Asp Asn Ala Asp 565 570 575 Thr Ile Thr Tyr Thr Ala Thr Val Lys Lys Asn Gly Val Ala Gln Ala 580 585 590 Asn Val Pro Val Ser Phe Asn Ile Val Ser Gly Thr Ala Thr Leu Gly 595 600 605 Ala Asn Ser Ala Lys Thr Asp Ala Asn Gly Lys Ala Thr Val Thr Leu 610 615 620 Lys Ser Ser Thr Pro Gly Gln Val Val Val Ser Ala Lys Thr Ala Glu 625 630 635 640 Met Thr Ser Ala Leu Asn Ala Ser Ala Val Ile Phe Phe Asp Gln Thr 645 650 655 Lys Ala Ser <210> SEQ ID NO 1502 <211> LENGTH: 235 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1502 Thr Ala Leu Thr Glu Gly Ala Lys Leu Phe Glu Lys Glu Ile Pro Tyr 1 5 10 15 Ile Thr Glu Leu Glu Gly Asp Val Glu Gly Met Lys Phe Ile Ile Lys 20 25 30 Gly Glu Gly Thr Gly Asp Ala Thr Thr Gly Thr Ile Lys Ala Lys Tyr 35 40 45 Ile Cys Thr Thr Gly Asp Leu Pro Val Pro Trp Ala Thr Leu Val Ser 50 55 60 Thr Leu Ser Tyr Gly Val Gln Cys Phe Ala Lys Tyr Pro Ser His Ile 65 70 75 80 Lys Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Thr Gln Glu Arg 85 90 95 Thr Ile Ser Phe Glu Gly Asp Gly Val Tyr Lys Thr Arg Ala Met Val 100 105 110 Thr Tyr Glu Arg Gly Ser Ile Tyr Asn Arg Val Thr Leu Thr Gly Glu 115 120 125 Asn Phe Lys Lys Asp Gly His Ile Leu Arg Lys Asn Val Ala Phe Gln 130 135 140 Cys Pro Pro Ser Ile Leu Tyr Ile Leu Pro Asp Thr Val Asn Asn Gly 145 150 155 160 Ile Arg Val Glu Phe Asn Gln Ala Tyr Asp Ile Glu Gly Val Thr Glu 165 170 175 Lys Leu Val Thr Lys Cys Ser Gln Met Asn Arg Pro Leu Ala Gly Ser 180 185 190 Ala Ala Val His Ile Pro Arg Tyr His His Ile Thr Tyr His Thr Lys 195 200 205 Leu Ser Lys Asp Arg Asp Glu Arg Arg Asp His Met Cys Leu Val Glu 210 215 220 Val Val Lys Ala Val Asp Leu Asp Thr Tyr Gln 225 230 235 <210> SEQ ID NO 1503 <211> LENGTH: 470 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1503 Thr Ala Leu Thr Glu Gly Ala Lys Leu Phe Glu Lys Glu Ile Pro Tyr 1 5 10 15 Ile Thr Glu Leu Glu Gly Asp Val Glu Gly Met Lys Phe Ile Ile Lys 20 25 30 Gly Glu Gly Thr Gly Asp Ala Thr Thr Gly Thr Ile Lys Ala Lys Tyr 35 40 45 Ile Cys Thr Thr Gly Asp Leu Pro Val Pro Trp Ala Thr Leu Val Ser 50 55 60 Thr Leu Ser Tyr Gly Val Gln Cys Phe Ala Lys Tyr Pro Ser His Ile 65 70 75 80 Lys Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Thr Gln Glu Arg 85 90 95 Thr Ile Ser Phe Glu Gly Asp Gly Val Tyr Lys Thr Arg Ala Met Val 100 105 110 Thr Tyr Glu Arg Gly Ser Ile Tyr Asn Arg Val Thr Leu Thr Gly Glu 115 120 125 Asn Phe Lys Lys Asp Gly His Ile Leu Arg Lys Asn Val Ala Phe Gln 130 135 140 Cys Pro Pro Ser Ile Leu Tyr Ile Leu Pro Asp Thr Val Asn Asn Gly 145 150 155 160 Ile Arg Val Glu Phe Asn Gln Ala Tyr Asp Ile Glu Gly Val Thr Glu 165 170 175 Lys Leu Val Thr Lys Cys Ser Gln Met Asn Arg Pro Leu Ala Gly Ser 180 185 190 Ala Ala Val His Ile Pro Arg Tyr His His Ile Thr Tyr His Thr Lys 195 200 205 Leu Ser Lys Asp Arg Asp Glu Arg Arg Asp His Met Cys Leu Val Glu 210 215 220 Val Val Lys Ala Val Asp Leu Asp Thr Tyr Gln Thr Ala Leu Thr Glu 225 230 235 240 Gly Ala Lys Leu Phe Glu Lys Glu Ile Pro Tyr Ile Thr Glu Leu Glu 245 250 255 Gly Asp Val Glu Gly Met Lys Phe Ile Ile Lys Gly Glu Gly Thr Gly 260 265 270 Asp Ala Thr Thr Gly Thr Ile Lys Ala Lys Tyr Ile Cys Thr Thr Gly 275 280 285 Asp Leu Pro Val Pro Trp Ala Thr Leu Val Ser Thr Leu Ser Tyr Gly 290 295 300 Val Gln Cys Phe Ala Lys Tyr Pro Ser His Ile Lys Asp Phe Phe Lys 305 310 315 320 Ser Ala Met Pro Glu Gly Tyr Thr Gln Glu Arg Thr Ile Ser Phe Glu 325 330 335 Gly Asp Gly Val Tyr Lys Thr Arg Ala Met Val Thr Tyr Glu Arg Gly 340 345 350 Ser Ile Tyr Asn Arg Val Thr Leu Thr Gly Glu Asn Phe Lys Lys Asp 355 360 365 Gly His Ile Leu Arg Lys Asn Val Ala Phe Gln Cys Pro Pro Ser Ile 370 375 380 Leu Tyr Ile Leu Pro Asp Thr Val Asn Asn Gly Ile Arg Val Glu Phe 385 390 395 400 Asn Gln Ala Tyr Asp Ile Glu Gly Val Thr Glu Lys Leu Val Thr Lys 405 410 415 Cys Ser Gln Met Asn Arg Pro Leu Ala Gly Ser Ala Ala Val His Ile 420 425 430 Pro Arg Tyr His His Ile Thr Tyr His Thr Lys Leu Ser Lys Asp Arg 435 440 445 Asp Glu Arg Arg Asp His Met Cys Leu Val Glu Val Val Lys Ala Val 450 455 460 Asp Leu Asp Thr Tyr Gln 465 470 <210> SEQ ID NO 1504 <211> LENGTH: 156 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1504 Ala Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly 1 5 10 15 Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser 20 25 30 Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe 35 40 45 Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser 50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val 65 70 75 80 Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr 85 90 95 Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr 100 105 110 Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Pro Ser 115 120 125 Thr Pro Pro Thr Pro Ser Pro Ser Thr Pro Pro Gly Leu Asn Asp Ile 130 135 140 Phe Glu Ala Gln Lys Ile Glu Trp His Gly Ser Ser 145 150 155 <210> SEQ ID NO 1505 <211> LENGTH: 149 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1505 Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala 1 5 10 15 Ala Gln Pro Ala Met Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly 20 25 30 Leu Val Glu Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 35 40 45 Ile Ile Phe Lys Ile Asn Asp Met Gly Trp Tyr Arg Gln Ala Pro Gly 50 55 60 Lys Arg Arg Glu Trp Val Ala Ala Ser Thr Gly Gly Asp Glu Ala Ile 65 70 75 80 Tyr Arg Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Ala Lys 85 90 95 Asn Ser Val Phe Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala 100 105 110 Val Tyr Tyr Cys Thr Ala Val Ile Ser Thr Asp Arg Asp Gly Thr Glu 115 120 125 Trp Arg Arg Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly 130 135 140 Gly Leu Pro Glu Thr 145 <210> SEQ ID NO 1506 <211> LENGTH: 70 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1506 tcataaaaaa tttatttgct ttcaggaaaa tttttctgta taatagattc ataaatttga 60 gagaggagtt 70 <210> SEQ ID NO 1507 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <220> FEATURE: <223> OTHER INFORMATION: See specification as filed for detailed description of substitutions and preferred embodiments <400> SEQUENCE: 1507 Gly Gly Gly Gly Ser 1 5 <210> SEQ ID NO 1508 <211> LENGTH: 656 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1508 Met Ile Thr His Gly Cys Tyr Thr Arg Thr Arg His Lys His Lys Leu 1 5 10 15 Lys Lys Thr Leu Ile Met Leu Ser Ala Gly Leu Gly Leu Phe Phe Tyr 20 25 30 Val Asn Gln Asn Ser Phe Ala Asn Gly Glu Asn Tyr Phe Lys Leu Gly 35 40 45 Ser Asp Ser Lys Leu Leu Thr His Asp Ser Tyr Gln Asn Arg Leu Phe 50 55 60 Tyr Thr Leu Lys Thr Gly Glu Thr Val Ala Asp Leu Ser Lys Ser Gln 65 70 75 80 Asp Ile Asn Leu Ser Thr Ile Trp Ser Leu Asn Lys His Leu Tyr Ser 85 90 95 Ser Glu Ser Glu Met Met Lys Ala Ala Pro Gly Gln Gln Ile Ile Leu 100 105 110 Pro Leu Lys Lys Leu Pro Phe Glu Tyr Ser Ala Leu Pro Leu Leu Gly 115 120 125 Ser Ala Pro Leu Val Ala Ala Gly Gly Val Ala Gly His Thr Asn Lys 130 135 140 Leu Thr Lys Met Ser Pro Asp Val Thr Lys Ser Asn Met Thr Asp Asp 145 150 155 160 Lys Ala Leu Asn Tyr Ala Ala Gln Gln Ala Ala Ser Leu Gly Ser Gln 165 170 175 Leu Gln Ser Arg Ser Leu Asn Gly Asp Tyr Ala Lys Asp Thr Ala Leu 180 185 190 Gly Ile Ala Gly Asn Gln Ala Ser Ser Gln Leu Gln Ala Trp Leu Gln 195 200 205 His Tyr Gly Thr Ala Glu Val Asn Leu Gln Ser Gly Asn Asn Phe Asp 210 215 220 Gly Ser Ser Leu Asp Phe Leu Leu Pro Phe Tyr Asp Ser Glu Lys Met 225 230 235 240 Leu Ala Phe Gly Gln Val Gly Ala Arg Tyr Ile Asp Ser Arg Phe Thr 245 250 255 Ala Asn Leu Gly Ala Gly Gln Arg Phe Phe Leu Pro Ala Asn Met Leu 260 265 270 Gly Tyr Asn Val Phe Ile Asp Gln Asp Phe Ser Gly Asp Asn Thr Arg 275 280 285 Leu Gly Ile Gly Gly Glu Tyr Trp Arg Asp Tyr Phe Lys Ser Ser Val 290 295 300 Asn Gly Tyr Phe Arg Met Ser Gly Trp His Glu Ser Tyr Asn Lys Lys 305 310 315 320 Asp Tyr Asp Glu Arg Pro Ala Asn Gly Phe Asp Ile Arg Phe Asn Gly 325 330 335 Tyr Leu Pro Ser Tyr Pro Ala Leu Gly Ala Lys Leu Ile Tyr Glu Gln 340 345 350 Tyr Tyr Gly Asp Asn Val Ala Leu Phe Asn Ser Asp Lys Leu Gln Ser 355 360 365 Asn Pro Gly Ala Ala Thr Val Gly Val Asn Tyr Thr Pro Ile Pro Leu 370 375 380 Val Thr Met Gly Ile Asp Tyr Arg His Gly Thr Gly Asn Glu Asn Asp 385 390 395 400 Leu Leu Tyr Ser Met Gln Phe Arg Tyr Gln Phe Asp Lys Ser Trp Ser 405 410 415 Gln Gln Ile Glu Pro Gln Tyr Val Asn Glu Leu Arg Thr Leu Ser Gly 420 425 430 Ser Arg Tyr Asp Leu Val Gln Arg Asn Asn Asn Ile Ile Leu Glu Tyr 435 440 445 Lys Lys Gln Asp Ile Leu Ser Leu Asn Ile Pro His Asp Ile Asn Gly 450 455 460 Thr Glu His Ser Thr Gln Lys Ile Gln Leu Ile Val Lys Ser Lys Tyr 465 470 475 480 Gly Leu Asp Arg Ile Val Trp Asp Asp Ser Ala Leu Arg Ser Gln Gly 485 490 495 Gly Gln Ile Gln His Ser Gly Ser Gln Ser Ala Gln Asp Tyr Gln Ala 500 505 510 Ile Leu Pro Ala Tyr Val Gln Gly Gly Ser Asn Ile Tyr Lys Val Thr 515 520 525 Ala Arg Ala Tyr Asp Arg Asn Gly Asn Ser Ser Asn Asn Val Gln Leu 530 535 540 Thr Ile Thr Val Leu Ser Asn Gly Gln Val Val Asp Gln Val Gly Val 545 550 555 560 Thr Asp Phe Thr Ala Asp Lys Thr Ser Ala Lys Ala Asp Asn Ala Asp 565 570 575 Thr Ile Thr Tyr Thr Ala Thr Val Lys Lys Asn Gly Val Ala Gln Ala 580 585 590 Asn Val Pro Val Ser Phe Asn Ile Val Ser Gly Thr Ala Thr Leu Gly 595 600 605 Ala Asn Ser Ala Lys Thr Asp Ala Asn Gly Lys Ala Thr Val Thr Leu 610 615 620 Lys Ser Ser Thr Pro Gly Gln Val Val Val Ser Ala Lys Thr Ala Glu 625 630 635 640 Met Thr Ser Ala Leu Asn Ala Ser Ala Val Ile Phe Phe Asp Gly Ala 645 650 655 <210> SEQ ID NO 1509 <211> LENGTH: 131 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1509 Met Ala Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Ala 1 5 10 15 Gly Gly Ser Leu Leu Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser 20 25 30 Ser Tyr Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu 35 40 45 Phe Val Ala Ala Ile Asn Trp Ser Gly Gly Ser Thr Ser Tyr Ala Asp 50 55 60 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Thr Lys Asn Thr 65 70 75 80 Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ala Phe 85 90 95 Tyr Cys Ala Ala Thr Tyr Asn Pro Tyr Ser Arg Asp His Tyr Phe Pro 100 105 110 Arg Met Thr Thr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr 115 120 125 Val Ser Ser 130 <210> SEQ ID NO 1510 <211> LENGTH: 139 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1510 Ala Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Ala Gly 1 5 10 15 Gly Ser Leu Leu Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser 20 25 30 Tyr Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe 35 40 45 Val Ala Ala Ile Asn Trp Ser Gly Gly Ser Thr Ser Tyr Ala Asp Ser 50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Thr Lys Asn Thr Val 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ala Phe Tyr 85 90 95 Cys Ala Ala Thr Tyr Asn Pro Tyr Ser Arg Asp His Tyr Phe Pro Arg 100 105 110 Met Thr Thr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val 115 120 125 Ser Ser Glu Pro Lys Thr Pro Lys Pro Gln Pro 130 135 <210> SEQ ID NO 1511 <211> LENGTH: 124 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1511 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr 20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val 35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp 100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 115 120

1 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 1511 <210> SEQ ID NO 1 <400> SEQUENCE: 1 000 <210> SEQ ID NO 2 <400> SEQUENCE: 2 000 <210> SEQ ID NO 3 <400> SEQUENCE: 3 000 <210> SEQ ID NO 4 <400> SEQUENCE: 4 000 <210> SEQ ID NO 5 <400> SEQUENCE: 5 000 <210> SEQ ID NO 6 <400> SEQUENCE: 6 000 <210> SEQ ID NO 7 <400> SEQUENCE: 7 000 <210> SEQ ID NO 8 <400> SEQUENCE: 8 000 <210> SEQ ID NO 9 <400> SEQUENCE: 9 000 <210> SEQ ID NO 10 <400> SEQUENCE: 10 000 <210> SEQ ID NO 11 <400> SEQUENCE: 11 000 <210> SEQ ID NO 12 <400> SEQUENCE: 12 000 <210> SEQ ID NO 13 <400> SEQUENCE: 13 000 <210> SEQ ID NO 14 <400> SEQUENCE: 14 000 <210> SEQ ID NO 15 <400> SEQUENCE: 15 000 <210> SEQ ID NO 16 <400> SEQUENCE: 16 000 <210> SEQ ID NO 17 <400> SEQUENCE: 17 000 <210> SEQ ID NO 18 <400> SEQUENCE: 18 000 <210> SEQ ID NO 19 <400> SEQUENCE: 19 000 <210> SEQ ID NO 20 <400> SEQUENCE: 20 000 <210> SEQ ID NO 21 <400> SEQUENCE: 21 000 <210> SEQ ID NO 22 <400> SEQUENCE: 22 000 <210> SEQ ID NO 23 <400> SEQUENCE: 23 000 <210> SEQ ID NO 24 <400> SEQUENCE: 24 000 <210> SEQ ID NO 25 <400> SEQUENCE: 25 000 <210> SEQ ID NO 26 <400> SEQUENCE: 26 000 <210> SEQ ID NO 27 <400> SEQUENCE: 27 000 <210> SEQ ID NO 28 <400> SEQUENCE: 28 000 <210> SEQ ID NO 29 <400> SEQUENCE: 29 000 <210> SEQ ID NO 30 <400> SEQUENCE: 30 000 <210> SEQ ID NO 31 <400> SEQUENCE: 31 000 <210> SEQ ID NO 32 <400> SEQUENCE: 32 000 <210> SEQ ID NO 33 <400> SEQUENCE: 33 000 <210> SEQ ID NO 34 <400> SEQUENCE: 34 000 <210> SEQ ID NO 35 <400> SEQUENCE: 35 000

<210> SEQ ID NO 36 <400> SEQUENCE: 36 000 <210> SEQ ID NO 37 <400> SEQUENCE: 37 000 <210> SEQ ID NO 38 <400> SEQUENCE: 38 000 <210> SEQ ID NO 39 <400> SEQUENCE: 39 000 <210> SEQ ID NO 40 <400> SEQUENCE: 40 000 <210> SEQ ID NO 41 <400> SEQUENCE: 41 000 <210> SEQ ID NO 42 <400> SEQUENCE: 42 000 <210> SEQ ID NO 43 <400> SEQUENCE: 43 000 <210> SEQ ID NO 44 <400> SEQUENCE: 44 000 <210> SEQ ID NO 45 <400> SEQUENCE: 45 000 <210> SEQ ID NO 46 <400> SEQUENCE: 46 000 <210> SEQ ID NO 47 <400> SEQUENCE: 47 000 <210> SEQ ID NO 48 <400> SEQUENCE: 48 000 <210> SEQ ID NO 49 <400> SEQUENCE: 49 000 <210> SEQ ID NO 50 <400> SEQUENCE: 50 000 <210> SEQ ID NO 51 <400> SEQUENCE: 51 000 <210> SEQ ID NO 52 <400> SEQUENCE: 52 000 <210> SEQ ID NO 53 <400> SEQUENCE: 53 000 <210> SEQ ID NO 54 <400> SEQUENCE: 54 000 <210> SEQ ID NO 55 <400> SEQUENCE: 55 000 <210> SEQ ID NO 56 <400> SEQUENCE: 56 000 <210> SEQ ID NO 57 <400> SEQUENCE: 57 000 <210> SEQ ID NO 58 <400> SEQUENCE: 58 000 <210> SEQ ID NO 59 <400> SEQUENCE: 59 000 <210> SEQ ID NO 60 <400> SEQUENCE: 60 000 <210> SEQ ID NO 61 <400> SEQUENCE: 61 000 <210> SEQ ID NO 62 <400> SEQUENCE: 62 000 <210> SEQ ID NO 63 <400> SEQUENCE: 63 000 <210> SEQ ID NO 64 <400> SEQUENCE: 64 000 <210> SEQ ID NO 65 <400> SEQUENCE: 65 000 <210> SEQ ID NO 66 <400> SEQUENCE: 66 000 <210> SEQ ID NO 67 <400> SEQUENCE: 67 000 <210> SEQ ID NO 68 <400> SEQUENCE: 68 000 <210> SEQ ID NO 69 <400> SEQUENCE: 69 000 <210> SEQ ID NO 70 <400> SEQUENCE: 70 000 <210> SEQ ID NO 71 <400> SEQUENCE: 71 000

<210> SEQ ID NO 72 <400> SEQUENCE: 72 000 <210> SEQ ID NO 73 <400> SEQUENCE: 73 000 <210> SEQ ID NO 74 <400> SEQUENCE: 74 000 <210> SEQ ID NO 75 <400> SEQUENCE: 75 000 <210> SEQ ID NO 76 <400> SEQUENCE: 76 000 <210> SEQ ID NO 77 <400> SEQUENCE: 77 000 <210> SEQ ID NO 78 <400> SEQUENCE: 78 000 <210> SEQ ID NO 79 <400> SEQUENCE: 79 000 <210> SEQ ID NO 80 <400> SEQUENCE: 80 000 <210> SEQ ID NO 81 <400> SEQUENCE: 81 000 <210> SEQ ID NO 82 <400> SEQUENCE: 82 000 <210> SEQ ID NO 83 <400> SEQUENCE: 83 000 <210> SEQ ID NO 84 <400> SEQUENCE: 84 000 <210> SEQ ID NO 85 <400> SEQUENCE: 85 000 <210> SEQ ID NO 86 <400> SEQUENCE: 86 000 <210> SEQ ID NO 87 <400> SEQUENCE: 87 000 <210> SEQ ID NO 88 <400> SEQUENCE: 88 000 <210> SEQ ID NO 89 <400> SEQUENCE: 89 000 <210> SEQ ID NO 90 <400> SEQUENCE: 90 000 <210> SEQ ID NO 91 <400> SEQUENCE: 91 000 <210> SEQ ID NO 92 <400> SEQUENCE: 92 000 <210> SEQ ID NO 93 <400> SEQUENCE: 93 000 <210> SEQ ID NO 94 <400> SEQUENCE: 94 000 <210> SEQ ID NO 95 <400> SEQUENCE: 95 000 <210> SEQ ID NO 96 <400> SEQUENCE: 96 000 <210> SEQ ID NO 97 <400> SEQUENCE: 97 000 <210> SEQ ID NO 98 <400> SEQUENCE: 98 000 <210> SEQ ID NO 99 <400> SEQUENCE: 99 000 <210> SEQ ID NO 100 <400> SEQUENCE: 100 000 <210> SEQ ID NO 101 <400> SEQUENCE: 101 000 <210> SEQ ID NO 102 <400> SEQUENCE: 102 000 <210> SEQ ID NO 103 <400> SEQUENCE: 103 000 <210> SEQ ID NO 104 <400> SEQUENCE: 104 000 <210> SEQ ID NO 105 <400> SEQUENCE: 105 000 <210> SEQ ID NO 106 <400> SEQUENCE: 106 000 <210> SEQ ID NO 107 <400> SEQUENCE: 107

000 <210> SEQ ID NO 108 <400> SEQUENCE: 108 000 <210> SEQ ID NO 109 <400> SEQUENCE: 109 000 <210> SEQ ID NO 110 <400> SEQUENCE: 110 000 <210> SEQ ID NO 111 <400> SEQUENCE: 111 000 <210> SEQ ID NO 112 <400> SEQUENCE: 112 000 <210> SEQ ID NO 113 <400> SEQUENCE: 113 000 <210> SEQ ID NO 114 <400> SEQUENCE: 114 000 <210> SEQ ID NO 115 <400> SEQUENCE: 115 000 <210> SEQ ID NO 116 <400> SEQUENCE: 116 000 <210> SEQ ID NO 117 <400> SEQUENCE: 117 000 <210> SEQ ID NO 118 <400> SEQUENCE: 118 000 <210> SEQ ID NO 119 <400> SEQUENCE: 119 000 <210> SEQ ID NO 120 <400> SEQUENCE: 120 000 <210> SEQ ID NO 121 <400> SEQUENCE: 121 000 <210> SEQ ID NO 122 <400> SEQUENCE: 122 000 <210> SEQ ID NO 123 <400> SEQUENCE: 123 000 <210> SEQ ID NO 124 <400> SEQUENCE: 124 000 <210> SEQ ID NO 125 <400> SEQUENCE: 125 000 <210> SEQ ID NO 126 <400> SEQUENCE: 126 000 <210> SEQ ID NO 127 <400> SEQUENCE: 127 000 <210> SEQ ID NO 128 <400> SEQUENCE: 128 000 <210> SEQ ID NO 129 <400> SEQUENCE: 129 000 <210> SEQ ID NO 130 <400> SEQUENCE: 130 000 <210> SEQ ID NO 131 <400> SEQUENCE: 131 000 <210> SEQ ID NO 132 <400> SEQUENCE: 132 000 <210> SEQ ID NO 133 <400> SEQUENCE: 133 000 <210> SEQ ID NO 134 <400> SEQUENCE: 134 000 <210> SEQ ID NO 135 <400> SEQUENCE: 135 000 <210> SEQ ID NO 136 <400> SEQUENCE: 136 000 <210> SEQ ID NO 137 <400> SEQUENCE: 137 000 <210> SEQ ID NO 138 <400> SEQUENCE: 138 000 <210> SEQ ID NO 139 <400> SEQUENCE: 139 000 <210> SEQ ID NO 140 <400> SEQUENCE: 140 000 <210> SEQ ID NO 141 <400> SEQUENCE: 141 000 <210> SEQ ID NO 142 <400> SEQUENCE: 142 000 <210> SEQ ID NO 143 <400> SEQUENCE: 143

000 <210> SEQ ID NO 144 <400> SEQUENCE: 144 000 <210> SEQ ID NO 145 <400> SEQUENCE: 145 000 <210> SEQ ID NO 146 <400> SEQUENCE: 146 000 <210> SEQ ID NO 147 <400> SEQUENCE: 147 000 <210> SEQ ID NO 148 <400> SEQUENCE: 148 000 <210> SEQ ID NO 149 <400> SEQUENCE: 149 000 <210> SEQ ID NO 150 <400> SEQUENCE: 150 000 <210> SEQ ID NO 151 <400> SEQUENCE: 151 000 <210> SEQ ID NO 152 <400> SEQUENCE: 152 000 <210> SEQ ID NO 153 <400> SEQUENCE: 153 000 <210> SEQ ID NO 154 <400> SEQUENCE: 154 000 <210> SEQ ID NO 155 <400> SEQUENCE: 155 000 <210> SEQ ID NO 156 <400> SEQUENCE: 156 000 <210> SEQ ID NO 157 <400> SEQUENCE: 157 000 <210> SEQ ID NO 158 <400> SEQUENCE: 158 000 <210> SEQ ID NO 159 <400> SEQUENCE: 159 000 <210> SEQ ID NO 160 <400> SEQUENCE: 160 000 <210> SEQ ID NO 161 <400> SEQUENCE: 161 000 <210> SEQ ID NO 162 <400> SEQUENCE: 162 000 <210> SEQ ID NO 163 <400> SEQUENCE: 163 000 <210> SEQ ID NO 164 <400> SEQUENCE: 164 000 <210> SEQ ID NO 165 <400> SEQUENCE: 165 000 <210> SEQ ID NO 166 <400> SEQUENCE: 166 000 <210> SEQ ID NO 167 <400> SEQUENCE: 167 000 <210> SEQ ID NO 168 <400> SEQUENCE: 168 000 <210> SEQ ID NO 169 <400> SEQUENCE: 169 000 <210> SEQ ID NO 170 <400> SEQUENCE: 170 000 <210> SEQ ID NO 171 <400> SEQUENCE: 171 000 <210> SEQ ID NO 172 <400> SEQUENCE: 172 000 <210> SEQ ID NO 173 <400> SEQUENCE: 173 000 <210> SEQ ID NO 174 <400> SEQUENCE: 174 000 <210> SEQ ID NO 175 <400> SEQUENCE: 175 000 <210> SEQ ID NO 176 <400> SEQUENCE: 176 000 <210> SEQ ID NO 177 <400> SEQUENCE: 177 000 <210> SEQ ID NO 178 <400> SEQUENCE: 178 000 <210> SEQ ID NO 179

<400> SEQUENCE: 179 000 <210> SEQ ID NO 180 <400> SEQUENCE: 180 000 <210> SEQ ID NO 181 <400> SEQUENCE: 181 000 <210> SEQ ID NO 182 <400> SEQUENCE: 182 000 <210> SEQ ID NO 183 <400> SEQUENCE: 183 000 <210> SEQ ID NO 184 <400> SEQUENCE: 184 000 <210> SEQ ID NO 185 <400> SEQUENCE: 185 000 <210> SEQ ID NO 186 <400> SEQUENCE: 186 000 <210> SEQ ID NO 187 <400> SEQUENCE: 187 000 <210> SEQ ID NO 188 <400> SEQUENCE: 188 000 <210> SEQ ID NO 189 <400> SEQUENCE: 189 000 <210> SEQ ID NO 190 <400> SEQUENCE: 190 000 <210> SEQ ID NO 191 <400> SEQUENCE: 191 000 <210> SEQ ID NO 192 <400> SEQUENCE: 192 000 <210> SEQ ID NO 193 <400> SEQUENCE: 193 000 <210> SEQ ID NO 194 <400> SEQUENCE: 194 000 <210> SEQ ID NO 195 <400> SEQUENCE: 195 000 <210> SEQ ID NO 196 <400> SEQUENCE: 196 000 <210> SEQ ID NO 197 <400> SEQUENCE: 197 000 <210> SEQ ID NO 198 <400> SEQUENCE: 198 000 <210> SEQ ID NO 199 <400> SEQUENCE: 199 000 <210> SEQ ID NO 200 <400> SEQUENCE: 200 000 <210> SEQ ID NO 201 <400> SEQUENCE: 201 000 <210> SEQ ID NO 202 <400> SEQUENCE: 202 000 <210> SEQ ID NO 203 <400> SEQUENCE: 203 000 <210> SEQ ID NO 204 <400> SEQUENCE: 204 000 <210> SEQ ID NO 205 <400> SEQUENCE: 205 000 <210> SEQ ID NO 206 <400> SEQUENCE: 206 000 <210> SEQ ID NO 207 <400> SEQUENCE: 207 000 <210> SEQ ID NO 208 <400> SEQUENCE: 208 000 <210> SEQ ID NO 209 <400> SEQUENCE: 209 000 <210> SEQ ID NO 210 <400> SEQUENCE: 210 000 <210> SEQ ID NO 211 <400> SEQUENCE: 211 000 <210> SEQ ID NO 212 <400> SEQUENCE: 212 000 <210> SEQ ID NO 213 <400> SEQUENCE: 213 000 <210> SEQ ID NO 214 <400> SEQUENCE: 214 000 <210> SEQ ID NO 215

<400> SEQUENCE: 215 000 <210> SEQ ID NO 216 <400> SEQUENCE: 216 000 <210> SEQ ID NO 217 <400> SEQUENCE: 217 000 <210> SEQ ID NO 218 <400> SEQUENCE: 218 000 <210> SEQ ID NO 219 <400> SEQUENCE: 219 000 <210> SEQ ID NO 220 <400> SEQUENCE: 220 000 <210> SEQ ID NO 221 <400> SEQUENCE: 221 000 <210> SEQ ID NO 222 <400> SEQUENCE: 222 000 <210> SEQ ID NO 223 <400> SEQUENCE: 223 000 <210> SEQ ID NO 224 <400> SEQUENCE: 224 000 <210> SEQ ID NO 225 <400> SEQUENCE: 225 000 <210> SEQ ID NO 226 <400> SEQUENCE: 226 000 <210> SEQ ID NO 227 <400> SEQUENCE: 227 000 <210> SEQ ID NO 228 <400> SEQUENCE: 228 000 <210> SEQ ID NO 229 <400> SEQUENCE: 229 000 <210> SEQ ID NO 230 <400> SEQUENCE: 230 000 <210> SEQ ID NO 231 <400> SEQUENCE: 231 000 <210> SEQ ID NO 232 <400> SEQUENCE: 232 000 <210> SEQ ID NO 233 <400> SEQUENCE: 233 000 <210> SEQ ID NO 234 <400> SEQUENCE: 234 000 <210> SEQ ID NO 235 <400> SEQUENCE: 235 000 <210> SEQ ID NO 236 <400> SEQUENCE: 236 000 <210> SEQ ID NO 237 <400> SEQUENCE: 237 000 <210> SEQ ID NO 238 <400> SEQUENCE: 238 000 <210> SEQ ID NO 239 <400> SEQUENCE: 239 000 <210> SEQ ID NO 240 <400> SEQUENCE: 240 000 <210> SEQ ID NO 241 <400> SEQUENCE: 241 000 <210> SEQ ID NO 242 <400> SEQUENCE: 242 000 <210> SEQ ID NO 243 <400> SEQUENCE: 243 000 <210> SEQ ID NO 244 <400> SEQUENCE: 244 000 <210> SEQ ID NO 245 <400> SEQUENCE: 245 000 <210> SEQ ID NO 246 <400> SEQUENCE: 246 000 <210> SEQ ID NO 247 <400> SEQUENCE: 247 000 <210> SEQ ID NO 248 <400> SEQUENCE: 248 000 <210> SEQ ID NO 249 <400> SEQUENCE: 249 000 <210> SEQ ID NO 250 <400> SEQUENCE: 250 000

<210> SEQ ID NO 251 <400> SEQUENCE: 251 000 <210> SEQ ID NO 252 <400> SEQUENCE: 252 000 <210> SEQ ID NO 253 <400> SEQUENCE: 253 000 <210> SEQ ID NO 254 <400> SEQUENCE: 254 000 <210> SEQ ID NO 255 <400> SEQUENCE: 255 000 <210> SEQ ID NO 256 <400> SEQUENCE: 256 000 <210> SEQ ID NO 257 <400> SEQUENCE: 257 000 <210> SEQ ID NO 258 <400> SEQUENCE: 258 000 <210> SEQ ID NO 259 <400> SEQUENCE: 259 000 <210> SEQ ID NO 260 <400> SEQUENCE: 260 000 <210> SEQ ID NO 261 <400> SEQUENCE: 261 000 <210> SEQ ID NO 262 <400> SEQUENCE: 262 000 <210> SEQ ID NO 263 <400> SEQUENCE: 263 000 <210> SEQ ID NO 264 <400> SEQUENCE: 264 000 <210> SEQ ID NO 265 <400> SEQUENCE: 265 000 <210> SEQ ID NO 266 <400> SEQUENCE: 266 000 <210> SEQ ID NO 267 <400> SEQUENCE: 267 000 <210> SEQ ID NO 268 <400> SEQUENCE: 268 000 <210> SEQ ID NO 269 <400> SEQUENCE: 269 000 <210> SEQ ID NO 270 <400> SEQUENCE: 270 000 <210> SEQ ID NO 271 <400> SEQUENCE: 271 000 <210> SEQ ID NO 272 <400> SEQUENCE: 272 000 <210> SEQ ID NO 273 <400> SEQUENCE: 273 000 <210> SEQ ID NO 274 <400> SEQUENCE: 274 000 <210> SEQ ID NO 275 <400> SEQUENCE: 275 000 <210> SEQ ID NO 276 <400> SEQUENCE: 276 000 <210> SEQ ID NO 277 <400> SEQUENCE: 277 000 <210> SEQ ID NO 278 <400> SEQUENCE: 278 000 <210> SEQ ID NO 279 <400> SEQUENCE: 279 000 <210> SEQ ID NO 280 <400> SEQUENCE: 280 000 <210> SEQ ID NO 281 <400> SEQUENCE: 281 000 <210> SEQ ID NO 282 <400> SEQUENCE: 282 000 <210> SEQ ID NO 283 <400> SEQUENCE: 283 000 <210> SEQ ID NO 284 <400> SEQUENCE: 284 000 <210> SEQ ID NO 285 <400> SEQUENCE: 285 000 <210> SEQ ID NO 286 <400> SEQUENCE: 286 000

<210> SEQ ID NO 287 <400> SEQUENCE: 287 000 <210> SEQ ID NO 288 <400> SEQUENCE: 288 000 <210> SEQ ID NO 289 <400> SEQUENCE: 289 000 <210> SEQ ID NO 290 <400> SEQUENCE: 290 000 <210> SEQ ID NO 291 <400> SEQUENCE: 291 000 <210> SEQ ID NO 292 <400> SEQUENCE: 292 000 <210> SEQ ID NO 293 <400> SEQUENCE: 293 000 <210> SEQ ID NO 294 <400> SEQUENCE: 294 000 <210> SEQ ID NO 295 <400> SEQUENCE: 295 000 <210> SEQ ID NO 296 <400> SEQUENCE: 296 000 <210> SEQ ID NO 297 <400> SEQUENCE: 297 000 <210> SEQ ID NO 298 <400> SEQUENCE: 298 000 <210> SEQ ID NO 299 <400> SEQUENCE: 299 000 <210> SEQ ID NO 300 <400> SEQUENCE: 300 000 <210> SEQ ID NO 301 <400> SEQUENCE: 301 000 <210> SEQ ID NO 302 <400> SEQUENCE: 302 000 <210> SEQ ID NO 303 <400> SEQUENCE: 303 000 <210> SEQ ID NO 304 <400> SEQUENCE: 304 000 <210> SEQ ID NO 305 <400> SEQUENCE: 305 000 <210> SEQ ID NO 306 <400> SEQUENCE: 306 000 <210> SEQ ID NO 307 <400> SEQUENCE: 307 000 <210> SEQ ID NO 308 <400> SEQUENCE: 308 000 <210> SEQ ID NO 309 <400> SEQUENCE: 309 000 <210> SEQ ID NO 310 <400> SEQUENCE: 310 000 <210> SEQ ID NO 311 <400> SEQUENCE: 311 000 <210> SEQ ID NO 312 <400> SEQUENCE: 312 000 <210> SEQ ID NO 313 <400> SEQUENCE: 313 000 <210> SEQ ID NO 314 <400> SEQUENCE: 314 000 <210> SEQ ID NO 315 <400> SEQUENCE: 315 000 <210> SEQ ID NO 316 <400> SEQUENCE: 316 000 <210> SEQ ID NO 317 <400> SEQUENCE: 317 000 <210> SEQ ID NO 318 <400> SEQUENCE: 318 000 <210> SEQ ID NO 319 <400> SEQUENCE: 319 000 <210> SEQ ID NO 320 <400> SEQUENCE: 320 000 <210> SEQ ID NO 321 <400> SEQUENCE: 321 000 <210> SEQ ID NO 322 <400> SEQUENCE: 322 000

<210> SEQ ID NO 323 <400> SEQUENCE: 323 000 <210> SEQ ID NO 324 <400> SEQUENCE: 324 000 <210> SEQ ID NO 325 <400> SEQUENCE: 325 000 <210> SEQ ID NO 326 <400> SEQUENCE: 326 000 <210> SEQ ID NO 327 <400> SEQUENCE: 327 000 <210> SEQ ID NO 328 <400> SEQUENCE: 328 000 <210> SEQ ID NO 329 <400> SEQUENCE: 329 000 <210> SEQ ID NO 330 <400> SEQUENCE: 330 000 <210> SEQ ID NO 331 <400> SEQUENCE: 331 000 <210> SEQ ID NO 332 <400> SEQUENCE: 332 000 <210> SEQ ID NO 333 <400> SEQUENCE: 333 000 <210> SEQ ID NO 334 <400> SEQUENCE: 334 000 <210> SEQ ID NO 335 <400> SEQUENCE: 335 000 <210> SEQ ID NO 336 <400> SEQUENCE: 336 000 <210> SEQ ID NO 337 <400> SEQUENCE: 337 000 <210> SEQ ID NO 338 <400> SEQUENCE: 338 000 <210> SEQ ID NO 339 <400> SEQUENCE: 339 000 <210> SEQ ID NO 340 <400> SEQUENCE: 340 000 <210> SEQ ID NO 341 <400> SEQUENCE: 341 000 <210> SEQ ID NO 342 <400> SEQUENCE: 342 000 <210> SEQ ID NO 343 <400> SEQUENCE: 343 000 <210> SEQ ID NO 344 <400> SEQUENCE: 344 000 <210> SEQ ID NO 345 <400> SEQUENCE: 345 000 <210> SEQ ID NO 346 <400> SEQUENCE: 346 000 <210> SEQ ID NO 347 <400> SEQUENCE: 347 000 <210> SEQ ID NO 348 <400> SEQUENCE: 348 000 <210> SEQ ID NO 349 <400> SEQUENCE: 349 000 <210> SEQ ID NO 350 <400> SEQUENCE: 350 000 <210> SEQ ID NO 351 <400> SEQUENCE: 351 000 <210> SEQ ID NO 352 <400> SEQUENCE: 352 000 <210> SEQ ID NO 353 <400> SEQUENCE: 353 000 <210> SEQ ID NO 354 <400> SEQUENCE: 354 000 <210> SEQ ID NO 355 <400> SEQUENCE: 355 000 <210> SEQ ID NO 356 <400> SEQUENCE: 356 000 <210> SEQ ID NO 357 <400> SEQUENCE: 357 000 <210> SEQ ID NO 358 <400> SEQUENCE: 358

000 <210> SEQ ID NO 359 <400> SEQUENCE: 359 000 <210> SEQ ID NO 360 <400> SEQUENCE: 360 000 <210> SEQ ID NO 361 <400> SEQUENCE: 361 000 <210> SEQ ID NO 362 <400> SEQUENCE: 362 000 <210> SEQ ID NO 363 <400> SEQUENCE: 363 000 <210> SEQ ID NO 364 <400> SEQUENCE: 364 000 <210> SEQ ID NO 365 <400> SEQUENCE: 365 000 <210> SEQ ID NO 366 <400> SEQUENCE: 366 000 <210> SEQ ID NO 367 <400> SEQUENCE: 367 000 <210> SEQ ID NO 368 <400> SEQUENCE: 368 000 <210> SEQ ID NO 369 <400> SEQUENCE: 369 000 <210> SEQ ID NO 370 <400> SEQUENCE: 370 000 <210> SEQ ID NO 371 <400> SEQUENCE: 371 000 <210> SEQ ID NO 372 <400> SEQUENCE: 372 000 <210> SEQ ID NO 373 <400> SEQUENCE: 373 000 <210> SEQ ID NO 374 <400> SEQUENCE: 374 000 <210> SEQ ID NO 375 <400> SEQUENCE: 375 000 <210> SEQ ID NO 376 <400> SEQUENCE: 376 000 <210> SEQ ID NO 377 <400> SEQUENCE: 377 000 <210> SEQ ID NO 378 <400> SEQUENCE: 378 000 <210> SEQ ID NO 379 <400> SEQUENCE: 379 000 <210> SEQ ID NO 380 <400> SEQUENCE: 380 000 <210> SEQ ID NO 381 <400> SEQUENCE: 381 000 <210> SEQ ID NO 382 <400> SEQUENCE: 382 000 <210> SEQ ID NO 383 <400> SEQUENCE: 383 000 <210> SEQ ID NO 384 <400> SEQUENCE: 384 000 <210> SEQ ID NO 385 <400> SEQUENCE: 385 000 <210> SEQ ID NO 386 <400> SEQUENCE: 386 000 <210> SEQ ID NO 387 <400> SEQUENCE: 387 000 <210> SEQ ID NO 388 <400> SEQUENCE: 388 000 <210> SEQ ID NO 389 <400> SEQUENCE: 389 000 <210> SEQ ID NO 390 <400> SEQUENCE: 390 000 <210> SEQ ID NO 391 <400> SEQUENCE: 391 000 <210> SEQ ID NO 392 <400> SEQUENCE: 392 000 <210> SEQ ID NO 393 <400> SEQUENCE: 393 000 <210> SEQ ID NO 394 <400> SEQUENCE: 394

000 <210> SEQ ID NO 395 <400> SEQUENCE: 395 000 <210> SEQ ID NO 396 <400> SEQUENCE: 396 000 <210> SEQ ID NO 397 <400> SEQUENCE: 397 000 <210> SEQ ID NO 398 <400> SEQUENCE: 398 000 <210> SEQ ID NO 399 <400> SEQUENCE: 399 000 <210> SEQ ID NO 400 <400> SEQUENCE: 400 000 <210> SEQ ID NO 401 <400> SEQUENCE: 401 000 <210> SEQ ID NO 402 <400> SEQUENCE: 402 000 <210> SEQ ID NO 403 <400> SEQUENCE: 403 000 <210> SEQ ID NO 404 <400> SEQUENCE: 404 000 <210> SEQ ID NO 405 <400> SEQUENCE: 405 000 <210> SEQ ID NO 406 <400> SEQUENCE: 406 000 <210> SEQ ID NO 407 <400> SEQUENCE: 407 000 <210> SEQ ID NO 408 <400> SEQUENCE: 408 000 <210> SEQ ID NO 409 <400> SEQUENCE: 409 000 <210> SEQ ID NO 410 <400> SEQUENCE: 410 000 <210> SEQ ID NO 411 <400> SEQUENCE: 411 000 <210> SEQ ID NO 412 <400> SEQUENCE: 412 000 <210> SEQ ID NO 413 <400> SEQUENCE: 413 000 <210> SEQ ID NO 414 <400> SEQUENCE: 414 000 <210> SEQ ID NO 415 <400> SEQUENCE: 415 000 <210> SEQ ID NO 416 <400> SEQUENCE: 416 000 <210> SEQ ID NO 417 <400> SEQUENCE: 417 000 <210> SEQ ID NO 418 <400> SEQUENCE: 418 000 <210> SEQ ID NO 419 <400> SEQUENCE: 419 000 <210> SEQ ID NO 420 <400> SEQUENCE: 420 000 <210> SEQ ID NO 421 <400> SEQUENCE: 421 000 <210> SEQ ID NO 422 <400> SEQUENCE: 422 000 <210> SEQ ID NO 423 <400> SEQUENCE: 423 000 <210> SEQ ID NO 424 <400> SEQUENCE: 424 000 <210> SEQ ID NO 425 <400> SEQUENCE: 425 000 <210> SEQ ID NO 426 <400> SEQUENCE: 426 000 <210> SEQ ID NO 427 <400> SEQUENCE: 427 000 <210> SEQ ID NO 428 <400> SEQUENCE: 428 000 <210> SEQ ID NO 429 <400> SEQUENCE: 429 000 <210> SEQ ID NO 430

<400> SEQUENCE: 430 000 <210> SEQ ID NO 431 <400> SEQUENCE: 431 000 <210> SEQ ID NO 432 <400> SEQUENCE: 432 000 <210> SEQ ID NO 433 <400> SEQUENCE: 433 000 <210> SEQ ID NO 434 <400> SEQUENCE: 434 000 <210> SEQ ID NO 435 <400> SEQUENCE: 435 000 <210> SEQ ID NO 436 <400> SEQUENCE: 436 000 <210> SEQ ID NO 437 <400> SEQUENCE: 437 000 <210> SEQ ID NO 438 <400> SEQUENCE: 438 000 <210> SEQ ID NO 439 <400> SEQUENCE: 439 000 <210> SEQ ID NO 440 <400> SEQUENCE: 440 000 <210> SEQ ID NO 441 <400> SEQUENCE: 441 000 <210> SEQ ID NO 442 <400> SEQUENCE: 442 000 <210> SEQ ID NO 443 <400> SEQUENCE: 443 000 <210> SEQ ID NO 444 <400> SEQUENCE: 444 000 <210> SEQ ID NO 445 <400> SEQUENCE: 445 000 <210> SEQ ID NO 446 <400> SEQUENCE: 446 000 <210> SEQ ID NO 447 <400> SEQUENCE: 447 000 <210> SEQ ID NO 448 <400> SEQUENCE: 448 000 <210> SEQ ID NO 449 <400> SEQUENCE: 449 000 <210> SEQ ID NO 450 <400> SEQUENCE: 450 000 <210> SEQ ID NO 451 <400> SEQUENCE: 451 000 <210> SEQ ID NO 452 <400> SEQUENCE: 452 000 <210> SEQ ID NO 453 <400> SEQUENCE: 453 000 <210> SEQ ID NO 454 <400> SEQUENCE: 454 000 <210> SEQ ID NO 455 <400> SEQUENCE: 455 000 <210> SEQ ID NO 456 <400> SEQUENCE: 456 000 <210> SEQ ID NO 457 <400> SEQUENCE: 457 000 <210> SEQ ID NO 458 <400> SEQUENCE: 458 000 <210> SEQ ID NO 459 <400> SEQUENCE: 459 000 <210> SEQ ID NO 460 <400> SEQUENCE: 460 000 <210> SEQ ID NO 461 <400> SEQUENCE: 461 000 <210> SEQ ID NO 462 <400> SEQUENCE: 462 000 <210> SEQ ID NO 463 <400> SEQUENCE: 463 000 <210> SEQ ID NO 464 <400> SEQUENCE: 464 000 <210> SEQ ID NO 465 <400> SEQUENCE: 465 000 <210> SEQ ID NO 466

<400> SEQUENCE: 466 000 <210> SEQ ID NO 467 <400> SEQUENCE: 467 000 <210> SEQ ID NO 468 <400> SEQUENCE: 468 000 <210> SEQ ID NO 469 <400> SEQUENCE: 469 000 <210> SEQ ID NO 470 <400> SEQUENCE: 470 000 <210> SEQ ID NO 471 <400> SEQUENCE: 471 000 <210> SEQ ID NO 472 <400> SEQUENCE: 472 000 <210> SEQ ID NO 473 <400> SEQUENCE: 473 000 <210> SEQ ID NO 474 <400> SEQUENCE: 474 000 <210> SEQ ID NO 475 <400> SEQUENCE: 475 000 <210> SEQ ID NO 476 <400> SEQUENCE: 476 000 <210> SEQ ID NO 477 <400> SEQUENCE: 477 000 <210> SEQ ID NO 478 <400> SEQUENCE: 478 000 <210> SEQ ID NO 479 <400> SEQUENCE: 479 000 <210> SEQ ID NO 480 <400> SEQUENCE: 480 000 <210> SEQ ID NO 481 <400> SEQUENCE: 481 000 <210> SEQ ID NO 482 <400> SEQUENCE: 482 000 <210> SEQ ID NO 483 <400> SEQUENCE: 483 000 <210> SEQ ID NO 484 <400> SEQUENCE: 484 000 <210> SEQ ID NO 485 <400> SEQUENCE: 485 000 <210> SEQ ID NO 486 <400> SEQUENCE: 486 000 <210> SEQ ID NO 487 <400> SEQUENCE: 487 000 <210> SEQ ID NO 488 <400> SEQUENCE: 488 000 <210> SEQ ID NO 489 <400> SEQUENCE: 489 000 <210> SEQ ID NO 490 <400> SEQUENCE: 490 000 <210> SEQ ID NO 491 <400> SEQUENCE: 491 000 <210> SEQ ID NO 492 <400> SEQUENCE: 492 000 <210> SEQ ID NO 493 <400> SEQUENCE: 493 000 <210> SEQ ID NO 494 <400> SEQUENCE: 494 000 <210> SEQ ID NO 495 <400> SEQUENCE: 495 000 <210> SEQ ID NO 496 <400> SEQUENCE: 496 000 <210> SEQ ID NO 497 <400> SEQUENCE: 497 000 <210> SEQ ID NO 498 <400> SEQUENCE: 498 000 <210> SEQ ID NO 499 <400> SEQUENCE: 499 000 <210> SEQ ID NO 500 <400> SEQUENCE: 500 000 <210> SEQ ID NO 501 <400> SEQUENCE: 501 000

<210> SEQ ID NO 502 <400> SEQUENCE: 502 000 <210> SEQ ID NO 503 <400> SEQUENCE: 503 000 <210> SEQ ID NO 504 <400> SEQUENCE: 504 000 <210> SEQ ID NO 505 <400> SEQUENCE: 505 000 <210> SEQ ID NO 506 <400> SEQUENCE: 506 000 <210> SEQ ID NO 507 <400> SEQUENCE: 507 000 <210> SEQ ID NO 508 <400> SEQUENCE: 508 000 <210> SEQ ID NO 509 <400> SEQUENCE: 509 000 <210> SEQ ID NO 510 <400> SEQUENCE: 510 000 <210> SEQ ID NO 511 <400> SEQUENCE: 511 000 <210> SEQ ID NO 512 <400> SEQUENCE: 512 000 <210> SEQ ID NO 513 <400> SEQUENCE: 513 000 <210> SEQ ID NO 514 <400> SEQUENCE: 514 000 <210> SEQ ID NO 515 <400> SEQUENCE: 515 000 <210> SEQ ID NO 516 <400> SEQUENCE: 516 000 <210> SEQ ID NO 517 <400> SEQUENCE: 517 000 <210> SEQ ID NO 518 <400> SEQUENCE: 518 000 <210> SEQ ID NO 519 <400> SEQUENCE: 519 000 <210> SEQ ID NO 520 <400> SEQUENCE: 520 000 <210> SEQ ID NO 521 <400> SEQUENCE: 521 000 <210> SEQ ID NO 522 <400> SEQUENCE: 522 000 <210> SEQ ID NO 523 <400> SEQUENCE: 523 000 <210> SEQ ID NO 524 <400> SEQUENCE: 524 000 <210> SEQ ID NO 525 <400> SEQUENCE: 525 000 <210> SEQ ID NO 526 <400> SEQUENCE: 526 000 <210> SEQ ID NO 527 <400> SEQUENCE: 527 000 <210> SEQ ID NO 528 <400> SEQUENCE: 528 000 <210> SEQ ID NO 529 <400> SEQUENCE: 529 000 <210> SEQ ID NO 530 <400> SEQUENCE: 530 000 <210> SEQ ID NO 531 <400> SEQUENCE: 531 000 <210> SEQ ID NO 532 <400> SEQUENCE: 532 000 <210> SEQ ID NO 533 <400> SEQUENCE: 533 000 <210> SEQ ID NO 534 <400> SEQUENCE: 534 000 <210> SEQ ID NO 535 <400> SEQUENCE: 535 000 <210> SEQ ID NO 536 <400> SEQUENCE: 536 000 <210> SEQ ID NO 537 <400> SEQUENCE: 537 000

<210> SEQ ID NO 538 <400> SEQUENCE: 538 000 <210> SEQ ID NO 539 <400> SEQUENCE: 539 000 <210> SEQ ID NO 540 <400> SEQUENCE: 540 000 <210> SEQ ID NO 541 <400> SEQUENCE: 541 000 <210> SEQ ID NO 542 <400> SEQUENCE: 542 000 <210> SEQ ID NO 543 <400> SEQUENCE: 543 000 <210> SEQ ID NO 544 <400> SEQUENCE: 544 000 <210> SEQ ID NO 545 <400> SEQUENCE: 545 000 <210> SEQ ID NO 546 <400> SEQUENCE: 546 000 <210> SEQ ID NO 547 <400> SEQUENCE: 547 000 <210> SEQ ID NO 548 <400> SEQUENCE: 548 000 <210> SEQ ID NO 549 <400> SEQUENCE: 549 000 <210> SEQ ID NO 550 <400> SEQUENCE: 550 000 <210> SEQ ID NO 551 <400> SEQUENCE: 551 000 <210> SEQ ID NO 552 <400> SEQUENCE: 552 000 <210> SEQ ID NO 553 <400> SEQUENCE: 553 000 <210> SEQ ID NO 554 <400> SEQUENCE: 554 000 <210> SEQ ID NO 555 <400> SEQUENCE: 555 000 <210> SEQ ID NO 556 <400> SEQUENCE: 556 000 <210> SEQ ID NO 557 <400> SEQUENCE: 557 000 <210> SEQ ID NO 558 <400> SEQUENCE: 558 000 <210> SEQ ID NO 559 <400> SEQUENCE: 559 000 <210> SEQ ID NO 560 <400> SEQUENCE: 560 000 <210> SEQ ID NO 561 <400> SEQUENCE: 561 000 <210> SEQ ID NO 562 <400> SEQUENCE: 562 000 <210> SEQ ID NO 563 <211> LENGTH: 290 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNR Responsive Promoter <400> SEQUENCE: 563 gtcagcataa caccctgacc tctcattaat tgttcatgcc gggcggcact atcgtcgtcc 60 ggccttttcc tctcttactc tgctacgtac atctatttct ataaatccgt tcaatttgtc 120 tgttttttgc acaaacatga aatatcagac aattccgtga cttaagaaaa tttatacaaa 180 tcagcaatat accccttaag gagtatataa aggtgaattt gatttacatc aataagcggg 240 gttgctgaat cgttaaggta ggcggtaata gaaaagaaat cgaggcaaaa 290 <210> SEQ ID NO 564 <211> LENGTH: 173 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNR Responsive Promoter <400> SEQUENCE: 564 atttcctctc atcccatccg gggtgagagt cttttccccc gacttatggc tcatgcatgc 60 atcaaaaaag atgtgagctt gatcaaaaac aaaaaatatt tcactcgaca ggagtattta 120 tattgcgccc gttacgtggg cttcgactgt aaatcagaaa ggagaaaaca cct 173 <210> SEQ ID NO 565 <211> LENGTH: 305 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNR Responsive Promoter <400> SEQUENCE: 565 gtcagcataa caccctgacc tctcattaat tgttcatgcc gggcggcact atcgtcgtcc 60 ggccttttcc tctcttactc tgctacgtac atctatttct ataaatccgt tcaatttgtc 120 tgttttttgc acaaacatga aatatcagac aattccgtga cttaagaaaa tttatacaaa 180 tcagcaatat accccttaag gagtatataa aggtgaattt gatttacatc aataagcggg 240 gttgctgaat cgttaaggat ccctctagaa ataattttgt ttaactttaa gaaggagata 300 tacat 305 <210> SEQ ID NO 566 <211> LENGTH: 180 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNR Responsive Promoter <400> SEQUENCE: 566 catttcctct catcccatcc ggggtgagag tcttttcccc cgacttatgg ctcatgcatg 60 catcaaaaaa gatgtgagct tgatcaaaaa caaaaaatat ttcactcgac aggagtattt 120 atattgcgcc cggatccctc tagaaataat tttgtttaac tttaagaagg agatatacat 180 <210> SEQ ID NO 567 <211> LENGTH: 199 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNR Responsive Promoter <400> SEQUENCE: 567 agttgttctt attggtggtg ttgctttatg gttgcatcgt agtaaatggt tgtaacaaaa 60 gcaatttttc cggctgtctg tatacaaaaa cgccgtaaag tttgagcgaa gtcaataaac 120 tctctaccca ttcagggcaa tatctctctt ggatccctct agaaataatt ttgtttaact 180 ttaagaagga gatatacat 199 <210> SEQ ID NO 568 <211> LENGTH: 117 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNR-responsive regulatory region <400> SEQUENCE: 568 atccccatca ctcttgatgg agatcaattc cccaagctgc tagagcgtta ccttgccctt 60 aaacattagc aatgtcgatt tatcagaggg ccgacaggct cccacaggag aaaaccg 117 <210> SEQ ID NO 569 <211> LENGTH: 108 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNR-responsive regulatory region <400> SEQUENCE: 569 ctcttgatcg ttatcaattc ccacgctgtt tcagagcgtt accttgccct taaacattag 60 caatgtcgat ttatcagagg gccgacaggc tcccacagga gaaaaccg 108 <210> SEQ ID NO 570 <211> LENGTH: 290 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: nirB1 , FNR-responsive regulatory region <400> SEQUENCE: 570 gtcagcataa caccctgacc tctcattaat tgttcatgcc gggcggcact atcgtcgtcc 60 ggccttttcc tctcttactc tgctacgtac atctatttct ataaatccgt tcaatttgtc 120 tgttttttgc acaaacatga aatatcagac aattccgtga cttaagaaaa tttatacaaa 180 tcagcaatat accccttaag gagtatataa aggtgaattt gatttacatc aataagcggg 240 gttgctgaat cgttaaggta ggcggtaata gaaaagaaat cgaggcaaaa 290 <210> SEQ ID NO 571 <211> LENGTH: 433 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: nirB2 , FNR-responsive regulatory region <400> SEQUENCE: 571 cggcccgatc gttgaacata gcggtccgca ggcggcactg cttacagcaa acggtctgta 60 cgctgtcgtc tttgtgatgt gcttcctgtt aggtttcgtc agccgtcacc gtcagcataa 120 caccctgacc tctcattaat tgctcatgcc ggacggcact atcgtcgtcc ggccttttcc 180 tctcttcccc cgctacgtgc atctatttct ataaacccgc tcattttgtc tattttttgc 240 acaaacatga aatatcagac aattccgtga cttaagaaaa tttatacaaa tcagcaatat 300 acccattaag gagtatataa aggtgaattt gatttacatc aataagcggg gttgctgaat 360 cgttaaggta ggcggtaata gaaaagaaat cgaggcaaaa atgtttgttt aactttaaga 420 aggagatata cat 433 <210> SEQ ID NO 572 <211> LENGTH: 290 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: nirB3 , FNR-responsive regulatory region <400> SEQUENCE: 572 gtcagcataa caccctgacc tctcattaat tgctcatgcc ggacggcact atcgtcgtcc 60 ggccttttcc tctcttcccc cgctacgtgc atctatttct ataaacccgc tcattttgtc 120 tattttttgc acaaacatga aatatcagac aattccgtga cttaagaaaa tttatacaaa 180 tcagcaatat acccattaag gagtatataa aggtgaattt gatttacatc aataagcggg 240 gttgctgaat cgttaaggta ggcggtaata gaaaagaaat cgaggcaaaa 290 <210> SEQ ID NO 573 <211> LENGTH: 173 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: ydfZ , FNR-responsive regulatory region <400> SEQUENCE: 573 atttcctctc atcccatccg gggtgagagt cttttccccc gacttatggc tcatgcatgc 60 atcaaaaaag atgtgagctt gatcaaaaac aaaaaatatt tcactcgaca ggagtattta 120 tattgcgccc gttacgtggg cttcgactgt aaatcagaaa ggagaaaaca cct 173 <210> SEQ ID NO 574 <211> LENGTH: 305 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: nirB+RBS , FNR-responsive regulatory region <400> SEQUENCE: 574 gtcagcataa caccctgacc tctcattaat tgttcatgcc gggcggcact atcgtcgtcc 60 ggccttttcc tctcttactc tgctacgtac atctatttct ataaatccgt tcaatttgtc 120 tgttttttgc acaaacatga aatatcagac aattccgtga cttaagaaaa tttatacaaa 180 tcagcaatat accccttaag gagtatataa aggtgaattt gatttacatc aataagcggg 240 gttgctgaat cgttaaggat ccctctagaa ataattttgt ttaactttaa gaaggagata 300 tacat 305 <210> SEQ ID NO 575 <211> LENGTH: 180 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: ydfZ+RBS , FNR-responsive regulatory region <400> SEQUENCE: 575 catttcctct catcccatcc ggggtgagag tcttttcccc cgacttatgg ctcatgcatg 60 catcaaaaaa gatgtgagct tgatcaaaaa caaaaaatat ttcactcgac aggagtattt 120 atattgcgcc cggatccctc tagaaataat tttgtttaac tttaagaagg agatatacat 180 <210> SEQ ID NO 576 <211> LENGTH: 199 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNRS1 , FNR-responsive regulatory region <400> SEQUENCE: 576 agttgttctt attggtggtg ttgctttatg gttgcatcgt agtaaatggt tgtaacaaaa 60 gcaatttttc cggctgtctg tatacaaaaa cgccgtaaag tttgagcgaa gtcaataaac 120 tctctaccca ttcagggcaa tatctctctt ggatccctct agaaataatt ttgtttaact 180 ttaagaagga gatatacat 199 <210> SEQ ID NO 577 <211> LENGTH: 207 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNRS2 , FNR-responsive regulatory region

<400> SEQUENCE: 577 agttgttctt attggtggtg ttgctttatg gttgcatcgt agtaaatggt tgtaacaaaa 60 gcaatttttc cggctgtctg tatacaaaaa cgccgcaaag tttgagcgaa gtcaataaac 120 tctctaccca ttcagggcaa tatctctctt ggatccaaag tgaactctag aaataatttt 180 gtttaacttt aagaaggaga tatacat 207 <210> SEQ ID NO 578 <211> LENGTH: 390 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: nirB+crp , FNR-responsive regulatory region <400> SEQUENCE: 578 tcgtctttgt gatgtgcttc ctgttaggtt tcgtcagccg tcaccgtcag cataacaccc 60 tgacctctca ttaattgctc atgccggacg gcactatcgt cgtccggcct tttcctctct 120 tcccccgcta cgtgcatcta tttctataaa cccgctcatt ttgtctattt tttgcacaaa 180 catgaaatat cagacaattc cgtgacttaa gaaaatttat acaaatcagc aatataccca 240 ttaaggagta tataaaggtg aatttgattt acatcaataa gcggggttgc tgaatcgtta 300 aggtagaaat gtgatctagt tcacatttgc ggtaatagaa aagaaatcga ggcaaaaatg 360 tttgtttaac tttaagaagg agatatacat 390 <210> SEQ ID NO 579 <211> LENGTH: 200 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: FNRS+crp , FNR-responsive regulatory region <400> SEQUENCE: 579 agttgttctt attggtggtg ttgctttatg gttgcatcgt agtaaatggt tgtaacaaaa 60 gcaatttttc cggctgtctg tatacaaaaa cgccgcaaag tttgagcgaa gtcaataaac 120 tctctaccca ttcagggcaa tatctctcaa atgtgatcta gttcacattt tttgtttaac 180 tttaagaagg agatatacat 200 <210> SEQ ID NO 580 <400> SEQUENCE: 580 000 <210> SEQ ID NO 581 <400> SEQUENCE: 581 000 <210> SEQ ID NO 582 <400> SEQUENCE: 582 000 <210> SEQ ID NO 583 <400> SEQUENCE: 583 000 <210> SEQ ID NO 584 <400> SEQUENCE: 584 000 <210> SEQ ID NO 585 <400> SEQUENCE: 585 000 <210> SEQ ID NO 586 <400> SEQUENCE: 586 000 <210> SEQ ID NO 587 <400> SEQUENCE: 587 000 <210> SEQ ID NO 588 <400> SEQUENCE: 588 000 <210> SEQ ID NO 589 <400> SEQUENCE: 589 000 <210> SEQ ID NO 590 <400> SEQUENCE: 590 000 <210> SEQ ID NO 591 <400> SEQUENCE: 591 000 <210> SEQ ID NO 592 <400> SEQUENCE: 592 000 <210> SEQ ID NO 593 <400> SEQUENCE: 593 000 <210> SEQ ID NO 594 <400> SEQUENCE: 594 000 <210> SEQ ID NO 595 <400> SEQUENCE: 595 000 <210> SEQ ID NO 596 <400> SEQUENCE: 596 000 <210> SEQ ID NO 597 <400> SEQUENCE: 597 000 <210> SEQ ID NO 598 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I14018 <400> SEQUENCE: 598 gtttatacat aggcgagtac tctgttatgg 30 <210> SEQ ID NO 599 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I14033 <400> SEQUENCE: 599 agaggttcca actttcacca taatgaaaca 30 <210> SEQ ID NO 600 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I14034 <400> SEQUENCE: 600 taaacaacta acggacaatt ctacctaaca 30 <210> SEQ ID NO 601 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I732021 <400> SEQUENCE: 601

acatcaagcc aaattaaaca ggattaacac 30 <210> SEQ ID NO 602 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I742126 <400> SEQUENCE: 602 gaggtaaaat agtcaacacg cacggtgtta 30 <210> SEQ ID NO 603 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J01006 <400> SEQUENCE: 603 caggccggaa taactcccta taatgcgcca 30 <210> SEQ ID NO 604 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23100 <400> SEQUENCE: 604 ggctagctca gtcctaggta cagtgctagc 30 <210> SEQ ID NO 605 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23101 <400> SEQUENCE: 605 agctagctca gtcctaggta ttatgctagc 30 <210> SEQ ID NO 606 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23102 <400> SEQUENCE: 606 agctagctca gtcctaggta ctgtgctagc 30 <210> SEQ ID NO 607 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23103 <400> SEQUENCE: 607 agctagctca gtcctaggga ttatgctagc 30 <210> SEQ ID NO 608 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23104 <400> SEQUENCE: 608 agctagctca gtcctaggta ttgtgctagc 30 <210> SEQ ID NO 609 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23105 <400> SEQUENCE: 609 ggctagctca gtcctaggta ctatgctagc 30 <210> SEQ ID NO 610 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23106 <400> SEQUENCE: 610 ggctagctca gtcctaggta tagtgctagc 30 <210> SEQ ID NO 611 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23107 <400> SEQUENCE: 611 ggctagctca gccctaggta ttatgctagc 30 <210> SEQ ID NO 612 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23108 <400> SEQUENCE: 612 agctagctca gtcctaggta taatgctagc 30 <210> SEQ ID NO 613 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23109 <400> SEQUENCE: 613 agctagctca gtcctaggga ctgtgctagc 30 <210> SEQ ID NO 614 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23110 <400> SEQUENCE: 614 ggctagctca gtcctaggta caatgctagc 30 <210> SEQ ID NO 615 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23111 <400> SEQUENCE: 615 ggctagctca gtcctaggta tagtgctagc 30 <210> SEQ ID NO 616 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23112 <400> SEQUENCE: 616 agctagctca gtcctaggga ttatgctagc 30 <210> SEQ ID NO 617 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide

<220> FEATURE: <223> OTHER INFORMATION: BBa_J23113 <400> SEQUENCE: 617 ggctagctca gtcctaggga ttatgctagc 30 <210> SEQ ID NO 618 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23114 <400> SEQUENCE: 618 ggctagctca gtcctaggta caatgctagc 30 <210> SEQ ID NO 619 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23115 <400> SEQUENCE: 619 agctagctca gcccttggta caatgctagc 30 <210> SEQ ID NO 620 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23116 <400> SEQUENCE: 620 agctagctca gtcctaggga ctatgctagc 30 <210> SEQ ID NO 621 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23117 <400> SEQUENCE: 621 agctagctca gtcctaggga ttgtgctagc 30 <210> SEQ ID NO 622 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23118 <400> SEQUENCE: 622 ggctagctca gtcctaggta ttgtgctagc 30 <210> SEQ ID NO 623 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23119 <400> SEQUENCE: 623 agctagctca gtcctaggta taatgctagc 30 <210> SEQ ID NO 624 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23150 <400> SEQUENCE: 624 ggctagctca gtcctaggta ttatgctagc 30 <210> SEQ ID NO 625 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J23151 <400> SEQUENCE: 625 ggctagctca gtcctaggta caatgctagc 30 <210> SEQ ID NO 626 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J44002 <400> SEQUENCE: 626 aaagtgtgac gccgtgcaaa taatcaatgt 30 <210> SEQ ID NO 627 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J48104 <400> SEQUENCE: 627 gacgaatact taaaatcgtc atacttattt 30 <210> SEQ ID NO 628 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J54200 <400> SEQUENCE: 628 aaacctttcg cggtatggca tgatagcgcc 30 <210> SEQ ID NO 629 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J56015 <400> SEQUENCE: 629 tgatagcgcc cggaagagag tcaattcagg 30 <210> SEQ ID NO 630 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J64951 <400> SEQUENCE: 630 ttatttaccg tgacgaacta attgctcgtg 30 <210> SEQ ID NO 631 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K088007 <400> SEQUENCE: 631 catacgccgt tatacgttgt ttacgctttg 30 <210> SEQ ID NO 632 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K119000 <400> SEQUENCE: 632 ttatgcttcc ggctcgtatg ttgtgtggac 30 <210> SEQ ID NO 633 <211> LENGTH: 30 <212> TYPE: DNA

<213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K119001 <400> SEQUENCE: 633 ttatgcttcc ggctcgtatg gtgtgtggac 30 <210> SEQ ID NO 634 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1330002 <400> SEQUENCE: 634 ggctagctca gtcctaggta ctatgctagc 30 <210> SEQ ID NO 635 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137029 <400> SEQUENCE: 635 atatatatat atatataatg gaagcgtttt 30 <210> SEQ ID NO 636 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137030 <400> SEQUENCE: 636 atatatatat atatataatg gaagcgtttt 30 <210> SEQ ID NO 637 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137031 <400> SEQUENCE: 637 ccccgaaagc ttaagaatat aattgtaagc 30 <210> SEQ ID NO 638 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137032 <400> SEQUENCE: 638 ccccgaaagc ttaagaatat aattgtaagc 30 <210> SEQ ID NO 639 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137085 <400> SEQUENCE: 639 tgacaatata tatatatata taatgctagc 30 <210> SEQ ID NO 640 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137086 <400> SEQUENCE: 640 acaatatata tatatatata taatgctagc 30 <210> SEQ ID NO 641 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137087 <400> SEQUENCE: 641 aatatatata tatatatata taatgctagc 30 <210> SEQ ID NO 642 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137088 <400> SEQUENCE: 642 tatatatata tatatatata taatgctagc 30 <210> SEQ ID NO 643 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137089 <400> SEQUENCE: 643 tatatatata tatatatata taatgctagc 30 <210> SEQ ID NO 644 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137090 <400> SEQUENCE: 644 aaaaaaaaaa aaaaaaaata taatgctagc 30 <210> SEQ ID NO 645 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K137091 <400> SEQUENCE: 645 aaaaaaaaaa aaaaaaaata taatgctagc 30 <210> SEQ ID NO 646 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585100 <400> SEQUENCE: 646 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 647 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585101 <400> SEQUENCE: 647 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 648 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585102 <400> SEQUENCE: 648 ggaattgtga gcggataaca atttcacaca 30

<210> SEQ ID NO 649 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585103 <400> SEQUENCE: 649 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 650 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585104 <400> SEQUENCE: 650 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 651 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585105 <400> SEQUENCE: 651 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 652 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585106 <400> SEQUENCE: 652 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 653 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585110 <400> SEQUENCE: 653 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 654 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585113 <400> SEQUENCE: 654 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 655 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585115 <400> SEQUENCE: 655 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 656 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585116 <400> SEQUENCE: 656 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 657 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585117 <400> SEQUENCE: 657 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 658 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585118 <400> SEQUENCE: 658 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 659 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1585119 <400> SEQUENCE: 659 ggaattgtga gcggataaca atttcacaca 30 <210> SEQ ID NO 660 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1824896 <400> SEQUENCE: 660 gattaaagag gagaaatact agagtactag 30 <210> SEQ ID NO 661 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K256002 <400> SEQUENCE: 661 caccttcggg tgggcctttc tgcgtttata 30 <210> SEQ ID NO 662 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K256018 <400> SEQUENCE: 662 caccttcggg tgggcctttc tgcgtttata 30 <210> SEQ ID NO 663 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K256020 <400> SEQUENCE: 663 caccttcggg tgggcctttc tgcgtttata 30 <210> SEQ ID NO 664 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE:

<223> OTHER INFORMATION: BBa_K256033 <400> SEQUENCE: 664 caccttcggg tgggcctttc tgcgtttata 30 <210> SEQ ID NO 665 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K292000 <400> SEQUENCE: 665 ggctagctca gtcctaggta cagtgctagc 30 <210> SEQ ID NO 666 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K292001 <400> SEQUENCE: 666 tgctagctac tagagattaa agaggagaaa 30 <210> SEQ ID NO 667 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K418000 <400> SEQUENCE: 667 ttgtgagcgg ataacaagat actgagcaca 30 <210> SEQ ID NO 668 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K418002 <400> SEQUENCE: 668 ttgtgagcgg ataacaagat actgagcaca 30 <210> SEQ ID NO 669 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K418003 <400> SEQUENCE: 669 ttgtgagcgg ataacaagat actgagcaca 30 <210> SEQ ID NO 670 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823004 <400> SEQUENCE: 670 ggctagctca gtcctaggta cagtgctagc 30 <210> SEQ ID NO 671 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823005 <400> SEQUENCE: 671 agctagctca gtcctaggta ttatgctagc 30 <210> SEQ ID NO 672 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823006 <400> SEQUENCE: 672 agctagctca gtcctaggta ctgtgctagc 30 <210> SEQ ID NO 673 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823007 <400> SEQUENCE: 673 agctagctca gtcctaggga ttatgctagc 30 <210> SEQ ID NO 674 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823008 <400> SEQUENCE: 674 ggctagctca gtcctaggta tagtgctagc 30 <210> SEQ ID NO 675 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823010 <400> SEQUENCE: 675 ggctagctca gtcctaggga ttatgctagc 30 <210> SEQ ID NO 676 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823011 <400> SEQUENCE: 676 ggctagctca gtcctaggta caatgctagc 30 <210> SEQ ID NO 677 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823013 <400> SEQUENCE: 677 agctagctca gtcctaggga ttgtgctagc 30 <210> SEQ ID NO 678 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823014 <400> SEQUENCE: 678 ggctagctca gtcctaggta ttgtgctagc 30 <210> SEQ ID NO 679 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13101 <400> SEQUENCE: 679 cctgttttta tgttattctc tctgtaaagg 30 <210> SEQ ID NO 680 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence

<220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13102 <400> SEQUENCE: 680 aaatatttgc ttatacaatc ttcctgtttt 30 <210> SEQ ID NO 681 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13103 <400> SEQUENCE: 681 gctgataaac cgatacaatt aaaggctcct 30 <210> SEQ ID NO 682 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13104 <400> SEQUENCE: 682 ctcttctcag cgtcttaatc taagctatcg 30 <210> SEQ ID NO 683 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13105 <400> SEQUENCE: 683 atgagccagt tcttaaaatc gcataaggta 30 <210> SEQ ID NO 684 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13106 <400> SEQUENCE: 684 ctattgattg tgacaaaata aacttattcc 30 <210> SEQ ID NO 685 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13108 <400> SEQUENCE: 685 gtttcgcgct tggtataatc gctgggggtc 30 <210> SEQ ID NO 686 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M13110 <400> SEQUENCE: 686 ctttgcttct gactataata gtcagggtaa 30 <210> SEQ ID NO 687 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M31519 <400> SEQUENCE: 687 aaaccgatac aattaaaggc tcctgctagc 30 <210> SEQ ID NO 688 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_R1074 <400> SEQUENCE: 688 caccacactg atagtgctag tgtagatcac 30 <210> SEQ ID NO 689 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_R1075 <400> SEQUENCE: 689 gccggaataa ctccctataa tgcgccacca 30 <210> SEQ ID NO 690 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_S03331 <400> SEQUENCE: 690 ttgacaagct tttcctcagc tccgtaaact 30 <210> SEQ ID NO 691 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J45992 <400> SEQUENCE: 691 ggtttcaaaa ttgtgatcta tatttaacaa 30 <210> SEQ ID NO 692 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J45993 <400> SEQUENCE: 692 ggtttcaaaa ttgtgatcta tatttaacaa 30 <210> SEQ ID NO 693 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J45504 <400> SEQUENCE: 693 tctattccaa taaagaaatc ttcctgcgtg 30 <210> SEQ ID NO 694 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1895002 <400> SEQUENCE: 694 gaccgaatat atagtggaaa cgtttagatg 30 <210> SEQ ID NO 695 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1895003 <400> SEQUENCE: 695 ccacatcctg tttttaacct taaaatggca 30

<210> SEQ ID NO 696 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K143012 <400> SEQUENCE: 696 aaaaatgggc tcgtgttgta caataaatgt 30 <210> SEQ ID NO 697 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K143013 <400> SEQUENCE: 697 aaaaaaagcg cgcgattatg taaaatataa 30 <210> SEQ ID NO 698 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K780003 <400> SEQUENCE: 698 aattgcagta ggcatgacaa aatggactca 30 <210> SEQ ID NO 699 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823000 <400> SEQUENCE: 699 caagcttttc ctttataata gaatgaatga 30 <210> SEQ ID NO 700 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823002 <400> SEQUENCE: 700 tctaagctag tgtattttgc gtttaatagt 30 <210> SEQ ID NO 701 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K823003 <400> SEQUENCE: 701 aatgggctcg tgttgtacaa taaatgtagt 30 <210> SEQ ID NO 702 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K143010 <400> SEQUENCE: 702 atccttatcg ttatgggtat tgtttgtaat 30 <210> SEQ ID NO 703 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K143011 <400> SEQUENCE: 703 taaaagaatt gtgagcggga atacaacaac 30 <210> SEQ ID NO 704 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K143013 <400> SEQUENCE: 704 aaaaaaagcg cgcgattatg taaaatataa 30 <210> SEQ ID NO 705 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K112706 <400> SEQUENCE: 705 tacaaaataa ttcccctgca aacattatca 30 <210> SEQ ID NO 706 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K112707 <400> SEQUENCE: 706 tacaaaataa ttcccctgca aacattatcg 30 <210> SEQ ID NO 707 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I712074 <400> SEQUENCE: 707 agggaataca agctacttgt tctttttgca 30 <210> SEQ ID NO 708 <211> LENGTH: 23 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I719005 <400> SEQUENCE: 708 taatacgact cactataggg aga 23 <210> SEQ ID NO 709 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J34814 <400> SEQUENCE: 709 gaatttaata cgactcacta tagggaga 28 <210> SEQ ID NO 710 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J64997 <400> SEQUENCE: 710 taatacgact cactatagg 19 <210> SEQ ID NO 711 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K113010

<400> SEQUENCE: 711 gagtcgtatt aatacgactc actatagggg 30 <210> SEQ ID NO 712 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K113011 <400> SEQUENCE: 712 agtgagtcgt actacgactc actatagggg 30 <210> SEQ ID NO 713 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K113012 <400> SEQUENCE: 713 gagtcgtatt aatacgactc tctatagggg 30 <210> SEQ ID NO 714 <211> LENGTH: 18 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K1614000 <400> SEQUENCE: 714 taatacgact cactatag 18 <210> SEQ ID NO 715 <211> LENGTH: 23 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_R0085 <400> SEQUENCE: 715 taatacgact cactataggg aga 23 <210> SEQ ID NO 716 <211> LENGTH: 23 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_R0180 <400> SEQUENCE: 716 ttatacgact cactataggg aga 23 <210> SEQ ID NO 717 <211> LENGTH: 23 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_R0181 <400> SEQUENCE: 717 gaatacgact cactataggg aga 23 <210> SEQ ID NO 718 <211> LENGTH: 23 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_R0182 <400> SEQUENCE: 718 taatacgtct cactataggg aga 23 <210> SEQ ID NO 719 <211> LENGTH: 23 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_R0183 <400> SEQUENCE: 719 tcatacgact cactataggg aga 23 <210> SEQ ID NO 720 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_Z0251 <400> SEQUENCE: 720 taatacgact cactataggg agaccacaac 30 <210> SEQ ID NO 721 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_Z0252 <400> SEQUENCE: 721 taattgaact cactaaaggg agaccacagc 30 <210> SEQ ID NO 722 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_Z0253 <400> SEQUENCE: 722 cgaagtaata cgactcacta ttagggaaga 30 <210> SEQ ID NO 723 <211> LENGTH: 19 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 723 atttaggtga cactataga 19 <210> SEQ ID NO 724 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I766555 <400> SEQUENCE: 724 acaaacacaa atacacacac taaattaata 30 <210> SEQ ID NO 725 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I766556 <400> SEQUENCE: 725 ccaagcatac aatcaactat ctcatataca 30 <210> SEQ ID NO 726 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I766557 <400> SEQUENCE: 726 gatacaggat acagcggaaa caacttttaa 30 <210> SEQ ID NO 727 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic

oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J63005 <400> SEQUENCE: 727 tttcaagcta taccaagcat acaatcaact 30 <210> SEQ ID NO 728 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K105027 <400> SEQUENCE: 728 cctttgcagc ataaattact atacttctat 30 <210> SEQ ID NO 729 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K105028 <400> SEQUENCE: 729 cctttgcagc ataaattact atacttctat 30 <210> SEQ ID NO 730 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K105029 <400> SEQUENCE: 730 cctttgcagc ataaattact atacttctat 30 <210> SEQ ID NO 731 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K105030 <400> SEQUENCE: 731 cctttgcagc ataaattact atacttctat 30 <210> SEQ ID NO 732 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K105031 <400> SEQUENCE: 732 cctttgcagc ataaattact atacttctat 30 <210> SEQ ID NO 733 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K122000 <400> SEQUENCE: 733 ttatctactt tttacaacaa atataaaaca 30 <210> SEQ ID NO 734 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K124000 <400> SEQUENCE: 734 acaaacacaa atacacacac taaattaata 30 <210> SEQ ID NO 735 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K124002 <400> SEQUENCE: 735 gtttcgaata aacacacata aacaaacaaa 30 <210> SEQ ID NO 736 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K319005 <400> SEQUENCE: 736 ccaagcatac aatcaactat ctcatataca 30 <210> SEQ ID NO 737 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_M31201 <400> SEQUENCE: 737 accatcaaag gaagctttaa tcttctcata 30 <210> SEQ ID NO 738 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_I712004 <400> SEQUENCE: 738 agaacccact gcttactggc ttatcgaaat 30 <210> SEQ ID NO 739 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_K076017 <400> SEQUENCE: 739 ggccgttttt ggcttttttg ttagacgaag 30 <210> SEQ ID NO 740 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: Plpp <400> SEQUENCE: 740 ataagtgcct tcccatcaaa aaaatattct caacataaaa aactttgtgt aatacttgta 60 acgcta 66 <210> SEQ ID NO 741 <211> LENGTH: 52 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: PapFAB46 <400> SEQUENCE: 741 aaaaagagta ttgacttcgc atctttttgt acctataata gattcattgc ta 52 <210> SEQ ID NO 742 <211> LENGTH: 59 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: PJ23101+UP element <400> SEQUENCE: 742 ggaaaatttt tttaaaaaaa aaactttaca gctagctcag tcctaggtat tatgctagc 59

<210> SEQ ID NO 743 <211> LENGTH: 59 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: PJ23107+UP element <400> SEQUENCE: 743 ggaaaatttt tttaaaaaaa aaactttacg gctagctcag ccctaggtat tatgctagc 59 <210> SEQ ID NO 744 <211> LENGTH: 64 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: PSYN23119 <400> SEQUENCE: 744 ggaaaatttt tttaaaaaaa aaacttgaca gctagctcag tccttggtat aatgctagca 60 cgaa 64 <210> SEQ ID NO 745 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <220> FEATURE: <223> OTHER INFORMATION: PhoA <400> SEQUENCE: 745 Met Lys Gln Ser Thr Ile Ala Leu Ala Leu Leu Pro Leu Leu Phe Thr 1 5 10 15 Pro Val Thr Lys Ala 20 <210> SEQ ID NO 746 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <220> FEATURE: <223> OTHER INFORMATION: PhoA <400> SEQUENCE: 746 Lys Gln Ser Thr Ile Ala Leu Ala Leu Leu Pro Leu Leu Phe Thr Pro 1 5 10 15 Val Thr Lys Ala 20 <210> SEQ ID NO 747 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <220> FEATURE: <223> OTHER INFORMATION: OmpF <400> SEQUENCE: 747 Met Met Lys Arg Asn Ile Leu Ala Val Ile Val Pro Ala Leu Leu Val 1 5 10 15 Ala Gly Thr Ala Asn Ala 20 <210> SEQ ID NO 748 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <220> FEATURE: <223> OTHER INFORMATION: cvaC <400> SEQUENCE: 748 Met Arg Thr Leu Thr Leu Asn Glu Leu Asp Ser Val Ser Gly Gly 1 5 10 15 <210> SEQ ID NO 749 <211> LENGTH: 43 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <220> FEATURE: <223> OTHER INFORMATION: TorA <400> SEQUENCE: 749 Met Asn Asn Asn Asp Leu Phe Gln Ala Ser Arg Arg Arg Phe Leu Ala 1 5 10 15 Gln Leu Gly Gly Leu Thr Val Ala Gly Met Leu Gly Thr Ser Leu Leu 20 25 30 Thr Pro Arg Arg Ala Thr Ala Ala Gln Ala Ala 35 40 <210> SEQ ID NO 750 <211> LENGTH: 33 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <220> FEATURE: <223> OTHER INFORMATION: fdnG <400> SEQUENCE: 750 Met Asp Val Ser Arg Arg Gln Phe Phe Lys Ile Cys Ala Gly Gly Met 1 5 10 15 Ala Gly Thr Thr Val Ala Ala Leu Gly Phe Ala Pro Lys Gln Ala Leu 20 25 30 Ala <210> SEQ ID NO 751 <211> LENGTH: 45 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <220> FEATURE: <223> OTHER INFORMATION: dmsA <400> SEQUENCE: 751 Met Lys Thr Lys Ile Pro Asp Ala Val Leu Ala Ala Glu Val Ser Arg 1 5 10 15 Arg Gly Leu Val Lys Thr Thr Ala Ile Gly Gly Leu Ala Met Ala Ser 20 25 30 Ser Ala Leu Thr Leu Pro Phe Ser Arg Ile Ala His Ala 35 40 45 <210> SEQ ID NO 752 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <220> FEATURE: <223> OTHER INFORMATION: PelB <400> SEQUENCE: 752 Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala Ala 1 5 10 15 Gln Pro Ala Met Ala 20 <210> SEQ ID NO 753 <211> LENGTH: 52 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <220> FEATURE: <223> OTHER INFORMATION: HlyA secretion signal <400> SEQUENCE: 753 Leu Asn Pro Leu Ile Asn Glu Ile Ser Lys Ile Ile Ser Ala Ala Gly 1 5 10 15 Asn Phe Asp Val Lys Glu Glu Arg Ala Ala Ala Ser Leu Leu Gln Leu 20 25 30 Ser Gly Asn Ala Ser Asp Phe Ser Tyr Gly Arg Asn Ser Ile Thr Leu 35 40 45 Thr Ala Ser Ala 50 <210> SEQ ID NO 754 <211> LENGTH: 159 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <220> FEATURE: <223> OTHER INFORMATION: HlyA secretion signal <400> SEQUENCE: 754 cttaatccat taattaatga aatcagcaaa atcatttcag ctgcaggtaa ttttgatgtt 60 aaagaggaaa gagctgcagc ttctttattg cagttgtccg gtaatgccag tgatttttca 120 tatggacgga actcaataac tttgacagca tcagcataa 159 <210> SEQ ID NO 755 <400> SEQUENCE: 755 000

<210> SEQ ID NO 756 <400> SEQUENCE: 756 000 <210> SEQ ID NO 757 <400> SEQUENCE: 757 000 <210> SEQ ID NO 758 <400> SEQUENCE: 758 000 <210> SEQ ID NO 759 <400> SEQUENCE: 759 000 <210> SEQ ID NO 760 <400> SEQUENCE: 760 000 <210> SEQ ID NO 761 <400> SEQUENCE: 761 000 <210> SEQ ID NO 762 <400> SEQUENCE: 762 000 <210> SEQ ID NO 763 <400> SEQUENCE: 763 000 <210> SEQ ID NO 764 <400> SEQUENCE: 764 000 <210> SEQ ID NO 765 <400> SEQUENCE: 765 000 <210> SEQ ID NO 766 <400> SEQUENCE: 766 000 <210> SEQ ID NO 767 <400> SEQUENCE: 767 000 <210> SEQ ID NO 768 <400> SEQUENCE: 768 000 <210> SEQ ID NO 769 <400> SEQUENCE: 769 000 <210> SEQ ID NO 770 <400> SEQUENCE: 770 000 <210> SEQ ID NO 771 <400> SEQUENCE: 771 000 <210> SEQ ID NO 772 <400> SEQUENCE: 772 000 <210> SEQ ID NO 773 <400> SEQUENCE: 773 000 <210> SEQ ID NO 774 <400> SEQUENCE: 774 000 <210> SEQ ID NO 775 <400> SEQUENCE: 775 000 <210> SEQ ID NO 776 <400> SEQUENCE: 776 000 <210> SEQ ID NO 777 <400> SEQUENCE: 777 000 <210> SEQ ID NO 778 <400> SEQUENCE: 778 000 <210> SEQ ID NO 779 <400> SEQUENCE: 779 000 <210> SEQ ID NO 780 <400> SEQUENCE: 780 000 <210> SEQ ID NO 781 <400> SEQUENCE: 781 000 <210> SEQ ID NO 782 <400> SEQUENCE: 782 000 <210> SEQ ID NO 783 <400> SEQUENCE: 783 000 <210> SEQ ID NO 784 <400> SEQUENCE: 784 000 <210> SEQ ID NO 785 <400> SEQUENCE: 785 000 <210> SEQ ID NO 786 <400> SEQUENCE: 786 000 <210> SEQ ID NO 787 <400> SEQUENCE: 787 000 <210> SEQ ID NO 788 <400> SEQUENCE: 788 000 <210> SEQ ID NO 789 <400> SEQUENCE: 789 000 <210> SEQ ID NO 790 <400> SEQUENCE: 790 000 <210> SEQ ID NO 791 <400> SEQUENCE: 791 000

<210> SEQ ID NO 792 <400> SEQUENCE: 792 000 <210> SEQ ID NO 793 <400> SEQUENCE: 793 000 <210> SEQ ID NO 794 <400> SEQUENCE: 794 000 <210> SEQ ID NO 795 <400> SEQUENCE: 795 000 <210> SEQ ID NO 796 <400> SEQUENCE: 796 000 <210> SEQ ID NO 797 <400> SEQUENCE: 797 000 <210> SEQ ID NO 798 <400> SEQUENCE: 798 000 <210> SEQ ID NO 799 <400> SEQUENCE: 799 000 <210> SEQ ID NO 800 <400> SEQUENCE: 800 000 <210> SEQ ID NO 801 <400> SEQUENCE: 801 000 <210> SEQ ID NO 802 <400> SEQUENCE: 802 000 <210> SEQ ID NO 803 <400> SEQUENCE: 803 000 <210> SEQ ID NO 804 <400> SEQUENCE: 804 000 <210> SEQ ID NO 805 <400> SEQUENCE: 805 000 <210> SEQ ID NO 806 <400> SEQUENCE: 806 000 <210> SEQ ID NO 807 <400> SEQUENCE: 807 000 <210> SEQ ID NO 808 <400> SEQUENCE: 808 000 <210> SEQ ID NO 809 <400> SEQUENCE: 809 000 <210> SEQ ID NO 810 <400> SEQUENCE: 810 000 <210> SEQ ID NO 811 <400> SEQUENCE: 811 000 <210> SEQ ID NO 812 <400> SEQUENCE: 812 000 <210> SEQ ID NO 813 <400> SEQUENCE: 813 000 <210> SEQ ID NO 814 <400> SEQUENCE: 814 000 <210> SEQ ID NO 815 <400> SEQUENCE: 815 000 <210> SEQ ID NO 816 <400> SEQUENCE: 816 000 <210> SEQ ID NO 817 <400> SEQUENCE: 817 000 <210> SEQ ID NO 818 <400> SEQUENCE: 818 000 <210> SEQ ID NO 819 <400> SEQUENCE: 819 000 <210> SEQ ID NO 820 <400> SEQUENCE: 820 000 <210> SEQ ID NO 821 <400> SEQUENCE: 821 000 <210> SEQ ID NO 822 <400> SEQUENCE: 822 000 <210> SEQ ID NO 823 <400> SEQUENCE: 823 000 <210> SEQ ID NO 824 <400> SEQUENCE: 824 000 <210> SEQ ID NO 825 <400> SEQUENCE: 825 000 <210> SEQ ID NO 826 <400> SEQUENCE: 826 000 <210> SEQ ID NO 827 <400> SEQUENCE: 827

000 <210> SEQ ID NO 828 <400> SEQUENCE: 828 000 <210> SEQ ID NO 829 <400> SEQUENCE: 829 000 <210> SEQ ID NO 830 <400> SEQUENCE: 830 000 <210> SEQ ID NO 831 <400> SEQUENCE: 831 000 <210> SEQ ID NO 832 <400> SEQUENCE: 832 000 <210> SEQ ID NO 833 <400> SEQUENCE: 833 000 <210> SEQ ID NO 834 <400> SEQUENCE: 834 000 <210> SEQ ID NO 835 <400> SEQUENCE: 835 000 <210> SEQ ID NO 836 <400> SEQUENCE: 836 000 <210> SEQ ID NO 837 <400> SEQUENCE: 837 000 <210> SEQ ID NO 838 <400> SEQUENCE: 838 000 <210> SEQ ID NO 839 <400> SEQUENCE: 839 000 <210> SEQ ID NO 840 <400> SEQUENCE: 840 000 <210> SEQ ID NO 841 <400> SEQUENCE: 841 000 <210> SEQ ID NO 842 <400> SEQUENCE: 842 000 <210> SEQ ID NO 843 <400> SEQUENCE: 843 000 <210> SEQ ID NO 844 <400> SEQUENCE: 844 000 <210> SEQ ID NO 845 <400> SEQUENCE: 845 000 <210> SEQ ID NO 846 <400> SEQUENCE: 846 000 <210> SEQ ID NO 847 <400> SEQUENCE: 847 000 <210> SEQ ID NO 848 <400> SEQUENCE: 848 000 <210> SEQ ID NO 849 <400> SEQUENCE: 849 000 <210> SEQ ID NO 850 <400> SEQUENCE: 850 000 <210> SEQ ID NO 851 <400> SEQUENCE: 851 000 <210> SEQ ID NO 852 <400> SEQUENCE: 852 000 <210> SEQ ID NO 853 <400> SEQUENCE: 853 000 <210> SEQ ID NO 854 <400> SEQUENCE: 854 000 <210> SEQ ID NO 855 <400> SEQUENCE: 855 000 <210> SEQ ID NO 856 <400> SEQUENCE: 856 000 <210> SEQ ID NO 857 <400> SEQUENCE: 857 000 <210> SEQ ID NO 858 <400> SEQUENCE: 858 000 <210> SEQ ID NO 859 <400> SEQUENCE: 859 000 <210> SEQ ID NO 860 <400> SEQUENCE: 860 000 <210> SEQ ID NO 861 <400> SEQUENCE: 861 000 <210> SEQ ID NO 862 <400> SEQUENCE: 862 000 <210> SEQ ID NO 863 <400> SEQUENCE: 863

000 <210> SEQ ID NO 864 <400> SEQUENCE: 864 000 <210> SEQ ID NO 865 <400> SEQUENCE: 865 000 <210> SEQ ID NO 866 <400> SEQUENCE: 866 000 <210> SEQ ID NO 867 <400> SEQUENCE: 867 000 <210> SEQ ID NO 868 <400> SEQUENCE: 868 000 <210> SEQ ID NO 869 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61133 <400> SEQUENCE: 869 tctagagaaa gacccgagac actagatg 28 <210> SEQ ID NO 870 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61134 <400> SEQUENCE: 870 tctagagaaa gaccggaaat actagatg 28 <210> SEQ ID NO 871 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61135 <400> SEQUENCE: 871 tctagagaaa gaccggagac actagatg 28 <210> SEQ ID NO 872 <400> SEQUENCE: 872 000 <210> SEQ ID NO 873 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61132 <400> SEQUENCE: 873 tctagagaaa gacaggatta actagatg 28 <210> SEQ ID NO 874 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61136 <400> SEQUENCE: 874 tctagagaaa gagctgagca actagatg 28 <210> SEQ ID NO 875 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61137 <400> SEQUENCE: 875 tctagagaaa gagtagatca actagatg 28 <210> SEQ ID NO 876 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61138 <400> SEQUENCE: 876 tctagagaaa gatatgaata actagatg 28 <210> SEQ ID NO 877 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61139 <400> SEQUENCE: 877 tctagagaaa gattagagtc actagatg 28 <210> SEQ ID NO 878 <400> SEQUENCE: 878 000 <210> SEQ ID NO 879 <400> SEQUENCE: 879 000 <210> SEQ ID NO 880 <211> LENGTH: 31 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0029 <400> SEQUENCE: 880 tctagagttc acacaggaaa cctactagat g 31 <210> SEQ ID NO 881 <211> LENGTH: 31 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0030 <400> SEQUENCE: 881 tctagagatt aaagaggaga aatactagat g 31 <210> SEQ ID NO 882 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0031 <400> SEQUENCE: 882 tctagagtca cacaggaaac ctactagatg 30 <210> SEQ ID NO 883 <211> LENGTH: 29 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0032 <400> SEQUENCE: 883 tctagagtca cacaggaaag tactagatg 29

<210> SEQ ID NO 884 <211> LENGTH: 27 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0033 <400> SEQUENCE: 884 tctagagtca cacaggacta ctagatg 27 <210> SEQ ID NO 885 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0034 <400> SEQUENCE: 885 tctagagaaa gaggagaaat actagatg 28 <210> SEQ ID NO 886 <211> LENGTH: 30 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0035 <400> SEQUENCE: 886 tctagagatt aaagaggaga atactagatg 30 <210> SEQ ID NO 887 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_B0064 <400> SEQUENCE: 887 tctagagaaa gaggggaaat actagatg 28 <210> SEQ ID NO 888 <400> SEQUENCE: 888 000 <210> SEQ ID NO 889 <400> SEQUENCE: 889 000 <210> SEQ ID NO 890 <400> SEQUENCE: 890 000 <210> SEQ ID NO 891 <400> SEQUENCE: 891 000 <210> SEQ ID NO 892 <400> SEQUENCE: 892 000 <210> SEQ ID NO 893 <400> SEQUENCE: 893 000 <210> SEQ ID NO 894 <400> SEQUENCE: 894 000 <210> SEQ ID NO 895 <400> SEQUENCE: 895 000 <210> SEQ ID NO 896 <400> SEQUENCE: 896 000 <210> SEQ ID NO 897 <400> SEQUENCE: 897 000 <210> SEQ ID NO 898 <400> SEQUENCE: 898 000 <210> SEQ ID NO 899 <400> SEQUENCE: 899 000 <210> SEQ ID NO 900 <400> SEQUENCE: 900 000 <210> SEQ ID NO 901 <400> SEQUENCE: 901 000 <210> SEQ ID NO 902 <400> SEQUENCE: 902 000 <210> SEQ ID NO 903 <400> SEQUENCE: 903 000 <210> SEQ ID NO 904 <400> SEQUENCE: 904 000 <210> SEQ ID NO 905 <400> SEQUENCE: 905 000 <210> SEQ ID NO 906 <400> SEQUENCE: 906 000 <210> SEQ ID NO 907 <400> SEQUENCE: 907 000 <210> SEQ ID NO 908 <400> SEQUENCE: 908 000 <210> SEQ ID NO 909 <400> SEQUENCE: 909 000 <210> SEQ ID NO 910 <400> SEQUENCE: 910 000 <210> SEQ ID NO 911 <400> SEQUENCE: 911 000 <210> SEQ ID NO 912 <400> SEQUENCE: 912 000 <210> SEQ ID NO 913 <400> SEQUENCE: 913 000 <210> SEQ ID NO 914 <400> SEQUENCE: 914

000 <210> SEQ ID NO 915 <400> SEQUENCE: 915 000 <210> SEQ ID NO 916 <400> SEQUENCE: 916 000 <210> SEQ ID NO 917 <400> SEQUENCE: 917 000 <210> SEQ ID NO 918 <400> SEQUENCE: 918 000 <210> SEQ ID NO 919 <400> SEQUENCE: 919 000 <210> SEQ ID NO 920 <400> SEQUENCE: 920 000 <210> SEQ ID NO 921 <400> SEQUENCE: 921 000 <210> SEQ ID NO 922 <400> SEQUENCE: 922 000 <210> SEQ ID NO 923 <400> SEQUENCE: 923 000 <210> SEQ ID NO 924 <400> SEQUENCE: 924 000 <210> SEQ ID NO 925 <400> SEQUENCE: 925 000 <210> SEQ ID NO 926 <400> SEQUENCE: 926 000 <210> SEQ ID NO 927 <400> SEQUENCE: 927 000 <210> SEQ ID NO 928 <400> SEQUENCE: 928 000 <210> SEQ ID NO 929 <400> SEQUENCE: 929 000 <210> SEQ ID NO 930 <400> SEQUENCE: 930 000 <210> SEQ ID NO 931 <400> SEQUENCE: 931 000 <210> SEQ ID NO 932 <400> SEQUENCE: 932 000 <210> SEQ ID NO 933 <400> SEQUENCE: 933 000 <210> SEQ ID NO 934 <400> SEQUENCE: 934 000 <210> SEQ ID NO 935 <400> SEQUENCE: 935 000 <210> SEQ ID NO 936 <400> SEQUENCE: 936 000 <210> SEQ ID NO 937 <400> SEQUENCE: 937 000 <210> SEQ ID NO 938 <400> SEQUENCE: 938 000 <210> SEQ ID NO 939 <400> SEQUENCE: 939 000 <210> SEQ ID NO 940 <400> SEQUENCE: 940 000 <210> SEQ ID NO 941 <400> SEQUENCE: 941 000 <210> SEQ ID NO 942 <400> SEQUENCE: 942 000 <210> SEQ ID NO 943 <400> SEQUENCE: 943 000 <210> SEQ ID NO 944 <400> SEQUENCE: 944 000 <210> SEQ ID NO 945 <400> SEQUENCE: 945 000 <210> SEQ ID NO 946 <400> SEQUENCE: 946 000 <210> SEQ ID NO 947 <400> SEQUENCE: 947 000 <210> SEQ ID NO 948 <400> SEQUENCE: 948 000 <210> SEQ ID NO 949 <400> SEQUENCE: 949 000 <210> SEQ ID NO 950 <400> SEQUENCE: 950

000 <210> SEQ ID NO 951 <400> SEQUENCE: 951 000 <210> SEQ ID NO 952 <400> SEQUENCE: 952 000 <210> SEQ ID NO 953 <400> SEQUENCE: 953 000 <210> SEQ ID NO 954 <400> SEQUENCE: 954 000 <210> SEQ ID NO 955 <400> SEQUENCE: 955 000 <210> SEQ ID NO 956 <400> SEQUENCE: 956 000 <210> SEQ ID NO 957 <400> SEQUENCE: 957 000 <210> SEQ ID NO 958 <400> SEQUENCE: 958 000 <210> SEQ ID NO 959 <400> SEQUENCE: 959 000 <210> SEQ ID NO 960 <400> SEQUENCE: 960 000 <210> SEQ ID NO 961 <400> SEQUENCE: 961 000 <210> SEQ ID NO 962 <400> SEQUENCE: 962 000 <210> SEQ ID NO 963 <400> SEQUENCE: 963 000 <210> SEQ ID NO 964 <400> SEQUENCE: 964 000 <210> SEQ ID NO 965 <400> SEQUENCE: 965 000 <210> SEQ ID NO 966 <400> SEQUENCE: 966 000 <210> SEQ ID NO 967 <400> SEQUENCE: 967 000 <210> SEQ ID NO 968 <400> SEQUENCE: 968 000 <210> SEQ ID NO 969 <400> SEQUENCE: 969 000 <210> SEQ ID NO 970 <400> SEQUENCE: 970 000 <210> SEQ ID NO 971 <400> SEQUENCE: 971 000 <210> SEQ ID NO 972 <400> SEQUENCE: 972 000 <210> SEQ ID NO 973 <400> SEQUENCE: 973 000 <210> SEQ ID NO 974 <400> SEQUENCE: 974 000 <210> SEQ ID NO 975 <400> SEQUENCE: 975 000 <210> SEQ ID NO 976 <400> SEQUENCE: 976 000 <210> SEQ ID NO 977 <400> SEQUENCE: 977 000 <210> SEQ ID NO 978 <400> SEQUENCE: 978 000 <210> SEQ ID NO 979 <211> LENGTH: 45 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: scFvLinker <400> SEQUENCE: 979 ggtggaggcg gctctggcgg tggtgggagt ggaggcggtg gcagt 45 <210> SEQ ID NO 980 <400> SEQUENCE: 980 000 <210> SEQ ID NO 981 <400> SEQUENCE: 981 000 <210> SEQ ID NO 982 <400> SEQUENCE: 982 000 <210> SEQ ID NO 983 <400> SEQUENCE: 983 000 <210> SEQ ID NO 984 <400> SEQUENCE: 984 000

<210> SEQ ID NO 985 <400> SEQUENCE: 985 000 <210> SEQ ID NO 986 <400> SEQUENCE: 986 000 <210> SEQ ID NO 987 <400> SEQUENCE: 987 000 <210> SEQ ID NO 988 <400> SEQUENCE: 988 000 <210> SEQ ID NO 989 <400> SEQUENCE: 989 000 <210> SEQ ID NO 990 <211> LENGTH: 607 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <220> FEATURE: <223> OTHER INFORMATION: Invasin display tag <400> SEQUENCE: 990 Met Val Phe Gln Pro Ile Ser Glu Phe Leu Leu Ile Arg Asn Ala Gly 1 5 10 15 Met Ser Met Tyr Phe Asn Lys Ile Ile Ser Phe Asn Ile Ile Ser Arg 20 25 30 Ile Val Ile Cys Ile Phe Leu Ile Cys Gly Met Phe Met Ala Gly Ala 35 40 45 Ser Glu Lys Tyr Asp Ala Asn Ala Pro Gln Gln Val Gln Pro Tyr Ser 50 55 60 Val Ser Ser Ser Ala Phe Glu Asn Leu His Pro Asn Asn Glu Met Glu 65 70 75 80 Ser Ser Ile Asn Pro Phe Ser Ala Ser Asp Thr Glu Arg Asn Ala Ala 85 90 95 Ile Ile Asp Arg Ala Asn Lys Glu Gln Glu Thr Glu Ala Val Asn Lys 100 105 110 Met Ile Ser Thr Gly Ala Arg Leu Ala Ala Ser Gly Arg Ala Ser Asp 115 120 125 Val Ala His Ser Met Val Gly Asp Ala Val Asn Gln Glu Ile Lys Gln 130 135 140 Trp Leu Asn Arg Phe Gly Thr Ala Gln Val Asn Leu Asn Phe Asp Lys 145 150 155 160 Asn Phe Ser Leu Lys Glu Ser Ser Leu Asp Trp Leu Ala Pro Trp Tyr 165 170 175 Asp Ser Ala Ser Phe Leu Phe Phe Ser Gln Leu Gly Ile Arg Asn Lys 180 185 190 Asp Ser Arg Asn Thr Leu Asn Leu Gly Val Gly Ile Arg Thr Leu Glu 195 200 205 Asn Gly Trp Leu Tyr Gly Leu Asn Thr Phe Tyr Asp Asn Asp Leu Thr 210 215 220 Gly His Asn His Arg Ile Gly Leu Gly Ala Glu Ala Trp Thr Asp Tyr 225 230 235 240 Leu Gln Leu Ala Ala Asn Gly Tyr Phe Arg Leu Asn Gly Trp His Ser 245 250 255 Ser Arg Asp Phe Ser Asp Tyr Lys Glu Arg Pro Ala Thr Gly Gly Asp 260 265 270 Leu Arg Ala Asn Ala Tyr Leu Pro Ala Leu Pro Gln Leu Gly Gly Lys 275 280 285 Leu Met Tyr Glu Gln Tyr Thr Gly Glu Arg Val Ala Leu Phe Gly Lys 290 295 300 Asp Asn Leu Gln Arg Asn Pro Tyr Ala Val Thr Ala Gly Ile Asn Tyr 305 310 315 320 Thr Pro Val Pro Leu Leu Thr Val Gly Val Asp Gln Arg Met Gly Lys 325 330 335 Ser Ser Lys His Glu Thr Gln Trp Asn Leu Gln Met Asn Tyr Arg Leu 340 345 350 Gly Glu Ser Phe Gln Ser Gln Leu Ser Pro Ser Ala Val Ala Gly Thr 355 360 365 Arg Leu Leu Ala Glu Ser Arg Tyr Asn Leu Val Asp Arg Asn Asn Asn 370 375 380 Ile Val Leu Glu Tyr Gln Lys Gln Gln Val Val Lys Leu Thr Leu Ser 385 390 395 400 Pro Ala Thr Ile Ser Gly Leu Pro Gly Gln Val Tyr Gln Val Asn Ala 405 410 415 Gln Val Gln Gly Ala Ser Ala Val Arg Glu Ile Val Trp Ser Asp Ala 420 425 430 Glu Leu Ile Ala Ala Gly Gly Thr Leu Thr Pro Leu Ser Thr Thr Gln 435 440 445 Phe Asn Leu Val Leu Pro Pro Tyr Lys Arg Thr Ala Gln Val Ser Arg 450 455 460 Val Thr Asp Asp Leu Thr Ala Asn Phe Tyr Ser Leu Ser Ala Leu Ala 465 470 475 480 Val Asp His Gln Gly Asn Arg Ser Asn Ser Phe Thr Leu Ser Val Thr 485 490 495 Val Gln Gln Pro Gln Leu Thr Leu Thr Ala Ala Val Ile Gly Asp Gly 500 505 510 Ala Pro Ala Asn Gly Lys Thr Ala Ile Thr Val Glu Phe Thr Val Ala 515 520 525 Asp Phe Glu Gly Lys Pro Leu Ala Gly Gln Glu Val Val Ile Thr Thr 530 535 540 Asn Asn Gly Ala Leu Pro Asn Lys Ile Thr Glu Lys Thr Asp Ala Asn 545 550 555 560 Gly Val Ala Arg Ile Ala Leu Thr Asn Thr Thr Asp Gly Val Thr Val 565 570 575 Val Thr Ala Glu Val Glu Gly Gln Arg Gln Ser Val Asp Thr His Phe 580 585 590 Val Lys Gly Thr Ile Ala Ala Asp Lys Ser Thr Leu Ala Ala Val 595 600 605 <210> SEQ ID NO 991 <211> LENGTH: 148 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <220> FEATURE: <223> OTHER INFORMATION: LppOmpA display tag <400> SEQUENCE: 991 Lys Ala Thr Lys Leu Val Leu Gly Ala Val Ile Leu Gly Ser Thr Leu 1 5 10 15 Leu Ala Gly Cys Ser Ser Asn Ala Lys Ile Asp Gln Gly Ile Asn Pro 20 25 30 Tyr Val Gly Phe Glu Met Gly Tyr Asp Trp Leu Gly Arg Met Pro Tyr 35 40 45 Lys Gly Ser Val Glu Asn Gly Ala Tyr Lys Ala Gln Gly Val Gln Leu 50 55 60 Thr Ala Lys Leu Gly Tyr Pro Ile Thr Asp Asp Leu Asp Ile Tyr Thr 65 70 75 80 Arg Leu Gly Gly Met Val Trp Arg Ala Asp Thr Lys Ser Asn Val Tyr 85 90 95 Gly Lys Asn His Asp Thr Gly Val Ser Pro Val Phe Ala Gly Gly Val 100 105 110 Glu Tyr Ala Ile Thr Pro Glu Ile Ala Thr Arg Leu Glu Tyr Gln Trp 115 120 125 Thr Asn Asn Ile Gly Asp Ala His Thr Ile Gly Thr Arg Pro Asp Asn 130 135 140 Gly Ile Pro Gly 145 <210> SEQ ID NO 992 <211> LENGTH: 658 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <220> FEATURE: <223> OTHER INFORMATION: IntiminN display tag <400> SEQUENCE: 992 Ile Thr His Gly Cys Tyr Thr Arg Thr Arg His Lys His Lys Leu Lys 1 5 10 15 Lys Thr Leu Ile Met Leu Ser Ala Gly Leu Gly Leu Phe Phe Tyr Val 20 25 30 Asn Gln Asn Ser Phe Ala Asn Gly Glu Asn Tyr Phe Lys Leu Gly Ser 35 40 45 Asp Ser Lys Leu Leu Thr His Asp Ser Tyr Gln Asn Arg Leu Phe Tyr 50 55 60 Thr Leu Lys Thr Gly Glu Thr Val Ala Asp Leu Ser Lys Ser Gln Asp 65 70 75 80 Ile Asn Leu Ser Thr Ile Trp Ser Leu Asn Lys His Leu Tyr Ser Ser 85 90 95 Glu Ser Glu Met Met Lys Ala Ala Pro Gly Gln Gln Ile Ile Leu Pro 100 105 110 Leu Lys Lys Leu Pro Phe Glu Tyr Ser Ala Leu Pro Leu Leu Gly Ser 115 120 125 Ala Pro Leu Val Ala Ala Gly Gly Val Ala Gly His Thr Asn Lys Leu 130 135 140 Thr Lys Met Ser Pro Asp Val Thr Lys Ser Asn Met Thr Asp Asp Lys 145 150 155 160 Ala Leu Asn Tyr Ala Ala Gln Gln Ala Ala Ser Leu Gly Ser Gln Leu

165 170 175 Gln Ser Arg Ser Leu Asn Gly Asp Tyr Ala Lys Asp Thr Ala Leu Gly 180 185 190 Ile Ala Gly Asn Gln Ala Ser Ser Gln Leu Gln Ala Trp Leu Gln His 195 200 205 Tyr Gly Thr Ala Glu Val Asn Leu Gln Ser Gly Asn Asn Phe Asp Gly 210 215 220 Ser Ser Leu Asp Phe Leu Leu Pro Phe Tyr Asp Ser Glu Lys Met Leu 225 230 235 240 Ala Phe Gly Gln Val Gly Ala Arg Tyr Ile Asp Ser Arg Phe Thr Ala 245 250 255 Asn Leu Gly Ala Gly Gln Arg Phe Phe Leu Pro Ala Asn Met Leu Gly 260 265 270 Tyr Asn Val Phe Ile Asp Gln Asp Phe Ser Gly Asp Asn Thr Arg Leu 275 280 285 Gly Ile Gly Gly Glu Tyr Trp Arg Asp Tyr Phe Lys Ser Ser Val Asn 290 295 300 Gly Tyr Phe Arg Met Ser Gly Trp His Glu Ser Tyr Asn Lys Lys Asp 305 310 315 320 Tyr Asp Glu Arg Pro Ala Asn Gly Phe Asp Ile Arg Phe Asn Gly Tyr 325 330 335 Leu Pro Ser Tyr Pro Ala Leu Gly Ala Lys Leu Ile Tyr Glu Gln Tyr 340 345 350 Tyr Gly Asp Asn Val Ala Leu Phe Asn Ser Asp Lys Leu Gln Ser Asn 355 360 365 Pro Gly Ala Ala Thr Val Gly Val Asn Tyr Thr Pro Ile Pro Leu Val 370 375 380 Thr Met Gly Ile Asp Tyr Arg His Gly Thr Gly Asn Glu Asn Asp Leu 385 390 395 400 Leu Tyr Ser Met Gln Phe Arg Tyr Gln Phe Asp Lys Ser Trp Ser Gln 405 410 415 Gln Ile Glu Pro Gln Tyr Val Asn Glu Leu Arg Thr Leu Ser Gly Ser 420 425 430 Arg Tyr Asp Leu Val Gln Arg Asn Asn Asn Ile Ile Leu Glu Tyr Lys 435 440 445 Lys Gln Asp Ile Leu Ser Leu Asn Ile Pro His Asp Ile Asn Gly Thr 450 455 460 Glu His Ser Thr Gln Lys Ile Gln Leu Ile Val Lys Ser Lys Tyr Gly 465 470 475 480 Leu Asp Arg Ile Val Trp Asp Asp Ser Ala Leu Arg Ser Gln Gly Gly 485 490 495 Gln Ile Gln His Ser Gly Ser Gln Ser Ala Gln Asp Tyr Gln Ala Ile 500 505 510 Leu Pro Ala Tyr Val Gln Gly Gly Ser Asn Ile Tyr Lys Val Thr Ala 515 520 525 Arg Ala Tyr Tyr Arg Asn Gly Asn Ser Ser Asn Asn Val Gln Leu Thr 530 535 540 Ile Thr Val Leu Ser Asn Gly Gln Val Val Asp Gln Val Gly Val Thr 545 550 555 560 Asp Phe Thr Ala Asp Lys Thr Ser Ala Lys Ala Asp Asn Ala Asp Thr 565 570 575 Ile Thr Tyr Thr Ala Thr Val Lys Lys Asn Gly Val Ala Gln Ala Asn 580 585 590 Val Pro Val Ser Phe Asn Ile Val Ser Gly Thr Ala Thr Leu Gly Ala 595 600 605 Asn Ser Ala Lys Thr Asp Ala Asn Gly Lys Ala Thr Val Thr Leu Lys 610 615 620 Ser Ser Thr Pro Gly Gln Val Val Val Ser Ala Lys Thr Ala Glu Met 625 630 635 640 Thr Ser Ala Leu Asn Ala Ser Ala Val Ile Phe Phe Asp Gln Thr Lys 645 650 655 Ala Ser <210> SEQ ID NO 993 <400> SEQUENCE: 993 000 <210> SEQ ID NO 994 <400> SEQUENCE: 994 000 <210> SEQ ID NO 995 <400> SEQUENCE: 995 000 <210> SEQ ID NO 996 <400> SEQUENCE: 996 000 <210> SEQ ID NO 997 <400> SEQUENCE: 997 000 <210> SEQ ID NO 998 <400> SEQUENCE: 998 000 <210> SEQ ID NO 999 <400> SEQUENCE: 999 000 <210> SEQ ID NO 1000 <400> SEQUENCE: 1000 000 <210> SEQ ID NO 1001 <400> SEQUENCE: 1001 000 <210> SEQ ID NO 1002 <400> SEQUENCE: 1002 000 <210> SEQ ID NO 1003 <400> SEQUENCE: 1003 000 <210> SEQ ID NO 1004 <400> SEQUENCE: 1004 000 <210> SEQ ID NO 1005 <400> SEQUENCE: 1005 000 <210> SEQ ID NO 1006 <400> SEQUENCE: 1006 000 <210> SEQ ID NO 1007 <400> SEQUENCE: 1007 000 <210> SEQ ID NO 1008 <400> SEQUENCE: 1008 000 <210> SEQ ID NO 1009 <400> SEQUENCE: 1009 000 <210> SEQ ID NO 1010 <400> SEQUENCE: 1010 000 <210> SEQ ID NO 1011 <400> SEQUENCE: 1011 000 <210> SEQ ID NO 1012 <400> SEQUENCE: 1012 000 <210> SEQ ID NO 1013 <400> SEQUENCE: 1013 000 <210> SEQ ID NO 1014 <400> SEQUENCE: 1014 000 <210> SEQ ID NO 1015

<400> SEQUENCE: 1015 000 <210> SEQ ID NO 1016 <400> SEQUENCE: 1016 000 <210> SEQ ID NO 1017 <400> SEQUENCE: 1017 000 <210> SEQ ID NO 1018 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: Master Sequence <220> FEATURE: <221> NAME/KEY: modified_base <222> LOCATION: (13)..(15) <223> OTHER INFORMATION: a, c, g or t <220> FEATURE: <221> NAME/KEY: modified_base <222> LOCATION: (18)..(20) <223> OTHER INFORMATION: a, c, g or t <400> SEQUENCE: 1018 tctagagaaa gannngannn actagatg 28 <210> SEQ ID NO 1019 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61100 <400> SEQUENCE: 1019 tctagagaaa gaggggacaa actagatg 28 <210> SEQ ID NO 1020 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61101 <400> SEQUENCE: 1020 tctagagaaa gacaggaccc actagatg 28 <210> SEQ ID NO 1021 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61102 <400> SEQUENCE: 1021 tctagagaaa gatccgatgt actagatg 28 <210> SEQ ID NO 1022 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61103 <400> SEQUENCE: 1022 tctagagaaa gattagacaa actagatg 28 <210> SEQ ID NO 1023 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61104 <400> SEQUENCE: 1023 tctagagaaa gaagggacag actagatg 28 <210> SEQ ID NO 1024 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61105 <400> SEQUENCE: 1024 tctagagaaa gacatgacgt actagatg 28 <210> SEQ ID NO 1025 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61106 <400> SEQUENCE: 1025 tctagagaaa gataggagac actagatg 28 <210> SEQ ID NO 1026 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61107 <400> SEQUENCE: 1026 tctagagaaa gaagagactc actagatg 28 <210> SEQ ID NO 1027 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61108 <400> SEQUENCE: 1027 tctagagaaa gacgagatat actagatg 28 <210> SEQ ID NO 1028 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61109 <400> SEQUENCE: 1028 tctagagaaa gactggagac actagatg 28 <210> SEQ ID NO 1029 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61110 <400> SEQUENCE: 1029 tctagagaaa gaggcgaatt actagatg 28 <210> SEQ ID NO 1030 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61111 <400> SEQUENCE: 1030 tctagagaaa gaggcgatac actagatg 28 <210> SEQ ID NO 1031 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61112 <400> SEQUENCE: 1031 tctagagaaa gaggtgacat actagatg 28

<210> SEQ ID NO 1032 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61113 <400> SEQUENCE: 1032 tctagagaaa gagtggaaaa actagatg 28 <210> SEQ ID NO 1033 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61114 <400> SEQUENCE: 1033 tctagagaaa gatgagaaga actagatg 28 <210> SEQ ID NO 1034 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61115 <400> SEQUENCE: 1034 tctagagaaa gaagggatac actagatg 28 <210> SEQ ID NO 1035 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61116 <400> SEQUENCE: 1035 tctagagaaa gacatgaggc actagatg 28 <210> SEQ ID NO 1036 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61117 <400> SEQUENCE: 1036 tctagagaaa gacatgagtt actagatg 28 <210> SEQ ID NO 1037 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61118 <400> SEQUENCE: 1037 tctagagaaa gagacgaatc actagatg 28 <210> SEQ ID NO 1038 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61119 <400> SEQUENCE: 1038 tctagagaaa gatttgatat actagatg 28 <210> SEQ ID NO 1039 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61120 <400> SEQUENCE: 1039 tctagagaaa gacgcgagaa actagatg 28 <210> SEQ ID NO 1040 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61121 <400> SEQUENCE: 1040 tctagagaaa gagacgagtc actagatg 28 <210> SEQ ID NO 1041 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61122 <400> SEQUENCE: 1041 tctagagaaa gagaggagcc actagatg 28 <210> SEQ ID NO 1042 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61123 <400> SEQUENCE: 1042 tctagagaaa gagatgacta actagatg 28 <210> SEQ ID NO 1043 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61124 <400> SEQUENCE: 1043 tctagagaaa gagccgacat actagatg 28 <210> SEQ ID NO 1044 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61125 <400> SEQUENCE: 1044 tctagagaaa gagccgagtt actagatg 28 <210> SEQ ID NO 1045 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61126 <400> SEQUENCE: 1045 tctagagaaa gaggtgactc actagatg 28 <210> SEQ ID NO 1046 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61127 <400> SEQUENCE: 1046 tctagagaaa gagtggaact actagatg 28 <210> SEQ ID NO 1047 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61128

<400> SEQUENCE: 1047 tctagagaaa gataggactc actagatg 28 <210> SEQ ID NO 1048 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61129 <400> SEQUENCE: 1048 tctagagaaa gattggacgt actagatg 28 <210> SEQ ID NO 1049 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61130 <400> SEQUENCE: 1049 tctagagaaa gaaacgacat actagatg 28 <210> SEQ ID NO 1050 <211> LENGTH: 28 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <220> FEATURE: <223> OTHER INFORMATION: BBa_J61131 <400> SEQUENCE: 1050 tctagagaaa gaaccgaatt actagatg 28 <210> SEQ ID NO 1051 <400> SEQUENCE: 1051 000 <210> SEQ ID NO 1052 <400> SEQUENCE: 1052 000 <210> SEQ ID NO 1053 <400> SEQUENCE: 1053 000 <210> SEQ ID NO 1054 <400> SEQUENCE: 1054 000 <210> SEQ ID NO 1055 <400> SEQUENCE: 1055 000 <210> SEQ ID NO 1056 <400> SEQUENCE: 1056 000 <210> SEQ ID NO 1057 <400> SEQUENCE: 1057 000 <210> SEQ ID NO 1058 <400> SEQUENCE: 1058 000 <210> SEQ ID NO 1059 <400> SEQUENCE: 1059 000 <210> SEQ ID NO 1060 <400> SEQUENCE: 1060 000 <210> SEQ ID NO 1061 <400> SEQUENCE: 1061 000 <210> SEQ ID NO 1062 <400> SEQUENCE: 1062 000 <210> SEQ ID NO 1063 <400> SEQUENCE: 1063 000 <210> SEQ ID NO 1064 <400> SEQUENCE: 1064 000 <210> SEQ ID NO 1065 <400> SEQUENCE: 1065 000 <210> SEQ ID NO 1066 <400> SEQUENCE: 1066 000 <210> SEQ ID NO 1067 <400> SEQUENCE: 1067 000 <210> SEQ ID NO 1068 <400> SEQUENCE: 1068 000 <210> SEQ ID NO 1069 <400> SEQUENCE: 1069 000 <210> SEQ ID NO 1070 <400> SEQUENCE: 1070 000 <210> SEQ ID NO 1071 <400> SEQUENCE: 1071 000 <210> SEQ ID NO 1072 <400> SEQUENCE: 1072 000 <210> SEQ ID NO 1073 <400> SEQUENCE: 1073 000 <210> SEQ ID NO 1074 <400> SEQUENCE: 1074 000 <210> SEQ ID NO 1075 <400> SEQUENCE: 1075 000 <210> SEQ ID NO 1076 <400> SEQUENCE: 1076 000 <210> SEQ ID NO 1077 <400> SEQUENCE: 1077 000 <210> SEQ ID NO 1078 <400> SEQUENCE: 1078 000 <210> SEQ ID NO 1079

<400> SEQUENCE: 1079 000 <210> SEQ ID NO 1080 <400> SEQUENCE: 1080 000 <210> SEQ ID NO 1081 <400> SEQUENCE: 1081 000 <210> SEQ ID NO 1082 <400> SEQUENCE: 1082 000 <210> SEQ ID NO 1083 <400> SEQUENCE: 1083 000 <210> SEQ ID NO 1084 <400> SEQUENCE: 1084 000 <210> SEQ ID NO 1085 <400> SEQUENCE: 1085 000 <210> SEQ ID NO 1086 <400> SEQUENCE: 1086 000 <210> SEQ ID NO 1087 <400> SEQUENCE: 1087 000 <210> SEQ ID NO 1088 <400> SEQUENCE: 1088 000 <210> SEQ ID NO 1089 <400> SEQUENCE: 1089 000 <210> SEQ ID NO 1090 <400> SEQUENCE: 1090 000 <210> SEQ ID NO 1091 <400> SEQUENCE: 1091 000 <210> SEQ ID NO 1092 <400> SEQUENCE: 1092 000 <210> SEQ ID NO 1093 <400> SEQUENCE: 1093 000 <210> SEQ ID NO 1094 <400> SEQUENCE: 1094 000 <210> SEQ ID NO 1095 <400> SEQUENCE: 1095 000 <210> SEQ ID NO 1096 <400> SEQUENCE: 1096 000 <210> SEQ ID NO 1097 <400> SEQUENCE: 1097 000 <210> SEQ ID NO 1098 <400> SEQUENCE: 1098 000 <210> SEQ ID NO 1099 <400> SEQUENCE: 1099 000 <210> SEQ ID NO 1100 <400> SEQUENCE: 1100 000 <210> SEQ ID NO 1101 <400> SEQUENCE: 1101 000 <210> SEQ ID NO 1102 <400> SEQUENCE: 1102 000 <210> SEQ ID NO 1103 <400> SEQUENCE: 1103 000 <210> SEQ ID NO 1104 <400> SEQUENCE: 1104 000 <210> SEQ ID NO 1105 <400> SEQUENCE: 1105 000 <210> SEQ ID NO 1106 <400> SEQUENCE: 1106 000 <210> SEQ ID NO 1107 <400> SEQUENCE: 1107 000 <210> SEQ ID NO 1108 <400> SEQUENCE: 1108 000 <210> SEQ ID NO 1109 <400> SEQUENCE: 1109 000 <210> SEQ ID NO 1110 <400> SEQUENCE: 1110 000 <210> SEQ ID NO 1111 <400> SEQUENCE: 1111 000 <210> SEQ ID NO 1112 <400> SEQUENCE: 1112 000 <210> SEQ ID NO 1113 <400> SEQUENCE: 1113 000 <210> SEQ ID NO 1114 <400> SEQUENCE: 1114 000 <210> SEQ ID NO 1115

<400> SEQUENCE: 1115 000 <210> SEQ ID NO 1116 <400> SEQUENCE: 1116 000 <210> SEQ ID NO 1117 <400> SEQUENCE: 1117 000 <210> SEQ ID NO 1118 <400> SEQUENCE: 1118 000 <210> SEQ ID NO 1119 <400> SEQUENCE: 1119 000 <210> SEQ ID NO 1120 <400> SEQUENCE: 1120 000 <210> SEQ ID NO 1121 <400> SEQUENCE: 1121 000 <210> SEQ ID NO 1122 <400> SEQUENCE: 1122 000 <210> SEQ ID NO 1123 <400> SEQUENCE: 1123 000 <210> SEQ ID NO 1124 <400> SEQUENCE: 1124 000 <210> SEQ ID NO 1125 <400> SEQUENCE: 1125 000 <210> SEQ ID NO 1126 <400> SEQUENCE: 1126 000 <210> SEQ ID NO 1127 <400> SEQUENCE: 1127 000 <210> SEQ ID NO 1128 <400> SEQUENCE: 1128 000 <210> SEQ ID NO 1129 <400> SEQUENCE: 1129 000 <210> SEQ ID NO 1130 <400> SEQUENCE: 1130 000 <210> SEQ ID NO 1131 <400> SEQUENCE: 1131 000 <210> SEQ ID NO 1132 <400> SEQUENCE: 1132 000 <210> SEQ ID NO 1133 <400> SEQUENCE: 1133 000 <210> SEQ ID NO 1134 <400> SEQUENCE: 1134 000 <210> SEQ ID NO 1135 <211> LENGTH: 24 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1135 Met Phe Lys Ser Thr Leu Ala Ala Met Ala Ala Val Phe Ala Leu Ser 1 5 10 15 Ala Leu Ser Pro Ala Ala Met Ala 20 <210> SEQ ID NO 1136 <400> SEQUENCE: 1136 000 <210> SEQ ID NO 1137 <400> SEQUENCE: 1137 000 <210> SEQ ID NO 1138 <400> SEQUENCE: 1138 000 <210> SEQ ID NO 1139 <400> SEQUENCE: 1139 000 <210> SEQ ID NO 1140 <400> SEQUENCE: 1140 000 <210> SEQ ID NO 1141 <211> LENGTH: 72 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1141 atgtttaagt ctacacttgc agccatggcc gcagtcttcg cactgtcagc cttgagtcct 60 gctgcaatgg ca 72 <210> SEQ ID NO 1142 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1142 atgaagcagg cgcttcgcgt tgcgtttggg ttccttatcc tgtgggcatc cgtacttcac 60 gcc 63 <210> SEQ ID NO 1143 <211> LENGTH: 54 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1143 atgcgcgtac tgttattcct tctgttgtct ctttttatgt tgcccgcttt cagt 54 <210> SEQ ID NO 1144 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1144 atgaagaaga ctgccatcgc tattgccgtc gcccttgcgg gtttcgcaac cgtggcgcaa 60

gca 63 <210> SEQ ID NO 1145 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1145 atgaaatatc tgcttccaac ggctgctgct ggcctgttgc ttcttgccgc ccagcctgcg 60 atggct 66 <210> SEQ ID NO 1146 <400> SEQUENCE: 1146 000 <210> SEQ ID NO 1147 <400> SEQUENCE: 1147 000 <210> SEQ ID NO 1148 <400> SEQUENCE: 1148 000 <210> SEQ ID NO 1149 <400> SEQUENCE: 1149 000 <210> SEQ ID NO 1150 <400> SEQUENCE: 1150 000 <210> SEQ ID NO 1151 <400> SEQUENCE: 1151 000 <210> SEQ ID NO 1152 <400> SEQUENCE: 1152 000 <210> SEQ ID NO 1153 <400> SEQUENCE: 1153 000 <210> SEQ ID NO 1154 <400> SEQUENCE: 1154 000 <210> SEQ ID NO 1155 <400> SEQUENCE: 1155 000 <210> SEQ ID NO 1156 <400> SEQUENCE: 1156 000 <210> SEQ ID NO 1157 <211> LENGTH: 99 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1157 atggggtaca aaatgaacat tagctcgctt cgcaaagcat tcatttttat gggggctgtt 60 gcagctttaa gccttgtcaa tgcccagtca gcgcttgcc 99 <210> SEQ ID NO 1158 <211> LENGTH: 57 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1158 atgaaaaaga tttggctggc tcttgccggt ttagtcctgg cattcagcgc aagcgcg 57 <210> SEQ ID NO 1159 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1159 atgaaacaga gcacaatcgc tttagccttg ctgcctcttc ttttcacgcc tgtcacgaag 60 gca 63 <210> SEQ ID NO 1160 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1160 atgaagcagg ctctgcgcgt ggcatttggg ttcctgatct tatgggcgtc cgtcttacac 60 gca 63 <210> SEQ ID NO 1161 <211> LENGTH: 78 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1161 atgaaaatca agacgggggc acgcattctt gccttgagcg ccttgacaac gatgatgttc 60 agtgcaagtg cattagcg 78 <210> SEQ ID NO 1162 <211> LENGTH: 69 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1162 atgaataaga aagtcttgac attgtcggcg gtcatggcct cgatgttgtt cggggcagca 60 gcccacgca 69 <210> SEQ ID NO 1163 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1163 atgatgaagc gtaacatctt agccgttatt gtccccgcat tgcttgtggc cgggacggct 60 aacgca 66 <210> SEQ ID NO 1164 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1164 atgaagaaga ctgccatcgc tattgccgtc gcccttgcgg gtttcgcaac cgtggcgcaa 60 gca 63 <210> SEQ ID NO 1165 <211> LENGTH: 54 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1165 atgcgcgtgt tattgttctt gctgctgagc ttgtttatgt taccagcttt cagt 54 <210> SEQ ID NO 1166 <211> LENGTH: 75 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1166 atgatgatta ccttacgcaa gttgcccctt gcggtagccg ttgctgctgg tgtgatgtcc 60 gcgcaagcaa tggct 75

<210> SEQ ID NO 1167 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1167 atgaaatatc ttcttccaac ggctgctgct ggtttattgc ttcttgccgc ccagcctgcg 60 atggct 66 <210> SEQ ID NO 1168 <400> SEQUENCE: 1168 000 <210> SEQ ID NO 1169 <400> SEQUENCE: 1169 000 <210> SEQ ID NO 1170 <400> SEQUENCE: 1170 000 <210> SEQ ID NO 1171 <400> SEQUENCE: 1171 000 <210> SEQ ID NO 1172 <400> SEQUENCE: 1172 000 <210> SEQ ID NO 1173 <400> SEQUENCE: 1173 000 <210> SEQ ID NO 1174 <400> SEQUENCE: 1174 000 <210> SEQ ID NO 1175 <400> SEQUENCE: 1175 000 <210> SEQ ID NO 1176 <400> SEQUENCE: 1176 000 <210> SEQ ID NO 1177 <400> SEQUENCE: 1177 000 <210> SEQ ID NO 1178 <400> SEQUENCE: 1178 000 <210> SEQ ID NO 1179 <400> SEQUENCE: 1179 000 <210> SEQ ID NO 1180 <211> LENGTH: 33 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1180 Met Gly Tyr Lys Met Asn Ile Ser Ser Leu Arg Lys Ala Phe Ile Phe 1 5 10 15 Met Gly Ala Val Ala Ala Leu Ser Leu Val Asn Ala Gln Ser Ala Leu 20 25 30 Ala <210> SEQ ID NO 1181 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1181 Met Lys Lys Ile Trp Leu Ala Leu Ala Gly Leu Val Leu Ala Phe Ser 1 5 10 15 Ala Ser Ala <210> SEQ ID NO 1182 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1182 Met Lys Gln Ser Thr Ile Ala Leu Ala Leu Leu Pro Leu Leu Phe Thr 1 5 10 15 Pro Val Thr Lys Ala 20 <210> SEQ ID NO 1183 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1183 Met Lys Gln Ala Leu Arg Val Ala Phe Gly Phe Leu Ile Leu Trp Ala 1 5 10 15 Ser Val Leu His Ala 20 <210> SEQ ID NO 1184 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1184 Met Lys Ile Lys Thr Gly Ala Arg Ile Leu Ala Leu Ser Ala Leu Thr 1 5 10 15 Thr Met Met Phe Ser Ala Ser Ala Leu Ala 20 25 <210> SEQ ID NO 1185 <211> LENGTH: 23 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1185 Met Asn Lys Lys Val Leu Thr Leu Ser Ala Val Met Ala Ser Met Leu 1 5 10 15 Phe Gly Ala Ala Ala His Ala 20 <210> SEQ ID NO 1186 <211> LENGTH: 26 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1186 Met Thr Asn Ile Thr Lys Arg Ser Leu Val Ala Ala Gly Val Leu Ala 1 5 10 15 Ala Leu Met Ala Gly Asn Val Ala Leu Ala 20 25 <210> SEQ ID NO 1187 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1187 Met Lys Lys Thr Ala Ile Ala Ile Ala Val Ala Leu Ala Gly Phe Ala 1 5 10 15 Thr Val Ala Gln Ala 20 <210> SEQ ID NO 1188 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1188 Met Arg Val Leu Leu Phe Leu Leu Leu Ser Leu Phe Met Leu Pro Ala 1 5 10 15 Phe Ser <210> SEQ ID NO 1189 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1189 Met Met Ile Thr Leu Arg Lys Leu Pro Leu Ala Val Ala Val Ala Ala 1 5 10 15 Gly Val Met Ser Ala Gln Ala Met Ala 20 25 <210> SEQ ID NO 1190 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1190 Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala 1 5 10 15 Ala Gln Pro Ala Met Ala 20 <210> SEQ ID NO 1191 <400> SEQUENCE: 1191 000 <210> SEQ ID NO 1192 <400> SEQUENCE: 1192 000 <210> SEQ ID NO 1193 <400> SEQUENCE: 1193 000 <210> SEQ ID NO 1194 <400> SEQUENCE: 1194 000 <210> SEQ ID NO 1195 <400> SEQUENCE: 1195 000 <210> SEQ ID NO 1196 <400> SEQUENCE: 1196 000 <210> SEQ ID NO 1197 <400> SEQUENCE: 1197 000 <210> SEQ ID NO 1198 <400> SEQUENCE: 1198 000 <210> SEQ ID NO 1199 <400> SEQUENCE: 1199 000 <210> SEQ ID NO 1200 <400> SEQUENCE: 1200 000 <210> SEQ ID NO 1201 <400> SEQUENCE: 1201 000 <210> SEQ ID NO 1202 <400> SEQUENCE: 1202 000 <210> SEQ ID NO 1203 <400> SEQUENCE: 1203 000 <210> SEQ ID NO 1204 <400> SEQUENCE: 1204 000 <210> SEQ ID NO 1205 <400> SEQUENCE: 1205 000 <210> SEQ ID NO 1206 <400> SEQUENCE: 1206 000 <210> SEQ ID NO 1207 <400> SEQUENCE: 1207 000 <210> SEQ ID NO 1208 <400> SEQUENCE: 1208 000 <210> SEQ ID NO 1209 <400> SEQUENCE: 1209 000 <210> SEQ ID NO 1210 <400> SEQUENCE: 1210 000 <210> SEQ ID NO 1211 <400> SEQUENCE: 1211 000 <210> SEQ ID NO 1212 <400> SEQUENCE: 1212 000 <210> SEQ ID NO 1213 <400> SEQUENCE: 1213 000 <210> SEQ ID NO 1214 <400> SEQUENCE: 1214 000 <210> SEQ ID NO 1215 <400> SEQUENCE: 1215 000 <210> SEQ ID NO 1216 <400> SEQUENCE: 1216 000 <210> SEQ ID NO 1217 <400> SEQUENCE: 1217 000 <210> SEQ ID NO 1218 <211> LENGTH: 52 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1218 Met Lys Arg His Leu Asn Thr Ser Tyr Arg Leu Val Trp Asn His Ile 1 5 10 15

Thr Gly Ala Phe Val Val Ala Ser Glu Leu Ala Arg Ala Arg Gly Lys 20 25 30 Arg Ala Gly Val Ala Val Ala Leu Ser Leu Ala Ala Ala Thr Ser Leu 35 40 45 Pro Ala Leu Ala 50 <210> SEQ ID NO 1219 <211> LENGTH: 53 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1219 Met Asn Lys Ile Phe Lys Val Ile Trp Asn Pro Ala Thr Gly Ser Tyr 1 5 10 15 Thr Val Ala Ser Glu Thr Ala Lys Ser Arg Gly Lys Lys Ser Gly Arg 20 25 30 Ser Lys Leu Leu Ile Ser Ala Leu Val Ala Gly Gly Leu Leu Ser Ser 35 40 45 Phe Gly Ala Ser Ala 50 <210> SEQ ID NO 1220 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1220 Met Gln Leu Arg Lys Pro Ala Thr Ala Ile Leu Ala Leu Ala Leu Ser 1 5 10 15 Ala Gly Leu Ala Gln Ala 20 <210> SEQ ID NO 1221 <211> LENGTH: 40 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1221 Met Phe Trp Arg Asp Met Thr Leu Ser Val Trp Arg Lys Lys Thr Thr 1 5 10 15 Gly Leu Lys Thr Lys Lys Arg Leu Leu Ala Leu Val Leu Ala Ala Ala 20 25 30 Leu Cys Ser Ser Pro Val Trp Ala 35 40 <210> SEQ ID NO 1222 <211> LENGTH: 159 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1222 atgaacaaga ttttcaaggt tatctggaac cccgcgacag gcagctacac tgtggcctcc 60 gaaaccgcta agtcgcgcgg caagaagtca ggacgttcaa agctgcttat ttctgcttta 120 gtagccggag gattactttc tagctttgga gcctcggca 159 <210> SEQ ID NO 1223 <211> LENGTH: 57 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1223 atgaaaaaaa tctggctggc attagcaggc ttagtcctgg cctttagtgc ctcggca 57 <210> SEQ ID NO 1224 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1224 atgcagttgc gcaagcctgc cacggcaatt ttagcattag ctctttctgc gggcttggcc 60 caggca 66 <210> SEQ ID NO 1225 <211> LENGTH: 120 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1225 atgttctggc gcgacatgac actgagcgtt tggcgtaaaa aaacaacggg actgaaaacc 60 aaaaagcgtt tgttagccct tgtcctggcg gcagccctgt gctcgtcccc ggtatgggca 120 <210> SEQ ID NO 1226 <211> LENGTH: 99 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1226 atgggataca agatgaacat ttcatcactt cgcaaagctt ttatcttcat gggtgccgtt 60 gctgctctgt cactggtcaa tgctcaatcg gccctggca 99 <210> SEQ ID NO 1227 <211> LENGTH: 78 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1227 atgaagatta aaacaggcgc tcgtattttg gccctgtctg cgcttacgac tatgatgttt 60 agtgcctcgg ccctggca 78 <210> SEQ ID NO 1228 <211> LENGTH: 78 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1228 atgacgaata tcactaaacg tagccttgtg gccgcggggg tcttggctgc attgatggct 60 ggcaatgttg ctctggca 78 <210> SEQ ID NO 1229 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1229 atgaaatatc tgttgcccac ggctgccgcg ggtctgctgc tgctggcagc gcaaccggct 60 atggca 66 <210> SEQ ID NO 1230 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1230 atgaagcaaa gtacgatcgc ccttgcgctg ttgccccttc ttttcacgcc cgtcaccaag 60 gca 63 <210> SEQ ID NO 1231 <400> SEQUENCE: 1231 000 <210> SEQ ID NO 1232 <400> SEQUENCE: 1232 000 <210> SEQ ID NO 1233 <400> SEQUENCE: 1233 000 <210> SEQ ID NO 1234 <400> SEQUENCE: 1234 000 <210> SEQ ID NO 1235 <400> SEQUENCE: 1235 000

<210> SEQ ID NO 1236 <400> SEQUENCE: 1236 000 <210> SEQ ID NO 1237 <400> SEQUENCE: 1237 000 <210> SEQ ID NO 1238 <400> SEQUENCE: 1238 000 <210> SEQ ID NO 1239 <400> SEQUENCE: 1239 000 <210> SEQ ID NO 1240 <400> SEQUENCE: 1240 000 <210> SEQ ID NO 1241 <400> SEQUENCE: 1241 000 <210> SEQ ID NO 1242 <400> SEQUENCE: 1242 000 <210> SEQ ID NO 1243 <400> SEQUENCE: 1243 000 <210> SEQ ID NO 1244 <400> SEQUENCE: 1244 000 <210> SEQ ID NO 1245 <400> SEQUENCE: 1245 000 <210> SEQ ID NO 1246 <400> SEQUENCE: 1246 000 <210> SEQ ID NO 1247 <400> SEQUENCE: 1247 000 <210> SEQ ID NO 1248 <400> SEQUENCE: 1248 000 <210> SEQ ID NO 1249 <400> SEQUENCE: 1249 000 <210> SEQ ID NO 1250 <211> LENGTH: 24 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1250 ggaaaatttt tttaaaaaaa aaac 24 <210> SEQ ID NO 1251 <400> SEQUENCE: 1251 000 <210> SEQ ID NO 1252 <400> SEQUENCE: 1252 000 <210> SEQ ID NO 1253 <211> LENGTH: 57 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1253 atgaagaaaa tttggctggc acttgccggt ttggtattag cgttttccgc ctcggca 57 <210> SEQ ID NO 1254 <211> LENGTH: 522 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 1254 Met Gln Pro Trp His Gly Lys Ala Met Gln Arg Ala Ser Glu Ala Gly 1 5 10 15 Ala Thr Ala Pro Lys Ala Ser Ala Arg Asn Ala Arg Gly Ala Pro Met 20 25 30 Asp Pro Thr Glu Ser Pro Ala Ala Pro Glu Ala Ala Leu Pro Lys Ala 35 40 45 Gly Lys Phe Gly Pro Ala Arg Lys Ser Gly Ser Arg Gln Lys Lys Ser 50 55 60 Ala Pro Asp Thr Gln Glu Arg Pro Pro Val Arg Ala Thr Gly Ala Arg 65 70 75 80 Ala Lys Lys Ala Pro Gln Arg Ala Gln Asp Thr Gln Pro Ser Asp Ala 85 90 95 Thr Ser Ala Pro Gly Ala Glu Gly Leu Glu Pro Pro Ala Ala Arg Glu 100 105 110 Pro Ala Leu Ser Arg Ala Gly Ser Cys Arg Gln Arg Gly Ala Arg Cys 115 120 125 Ser Thr Lys Pro Arg Pro Pro Pro Gly Pro Trp Asp Val Pro Ser Pro 130 135 140 Gly Leu Pro Val Ser Ala Pro Ile Leu Val Arg Arg Asp Ala Ala Pro 145 150 155 160 Gly Ala Ser Lys Leu Arg Ala Val Leu Glu Lys Leu Lys Leu Ser Arg 165 170 175 Asp Asp Ile Ser Thr Ala Ala Gly Met Val Lys Gly Val Val Asp His 180 185 190 Leu Leu Leu Arg Leu Lys Cys Asp Ser Ala Phe Arg Gly Val Gly Leu 195 200 205 Leu Asn Thr Gly Ser Tyr Tyr Glu His Val Lys Ile Ser Ala Pro Asn 210 215 220 Glu Phe Asp Val Met Phe Lys Leu Glu Val Pro Arg Ile Gln Leu Glu 225 230 235 240 Glu Tyr Ser Asn Thr Arg Ala Tyr Tyr Phe Val Lys Phe Lys Arg Asn 245 250 255 Pro Lys Glu Asn Pro Leu Ser Gln Phe Leu Glu Gly Glu Ile Leu Ser 260 265 270 Ala Ser Lys Met Leu Ser Lys Phe Arg Lys Ile Ile Lys Glu Glu Ile 275 280 285 Asn Asp Ile Lys Asp Thr Asp Val Ile Met Lys Arg Lys Arg Gly Gly 290 295 300 Ser Pro Ala Val Thr Leu Leu Ile Ser Glu Lys Ile Ser Val Asp Ile 305 310 315 320 Thr Leu Ala Leu Glu Ser Lys Ser Ser Trp Pro Ala Ser Thr Gln Glu 325 330 335 Gly Leu Arg Ile Gln Asn Trp Leu Ser Ala Lys Val Arg Lys Gln Leu 340 345 350 Arg Leu Lys Pro Phe Tyr Leu Val Pro Lys His Ala Lys Glu Gly Asn 355 360 365 Gly Phe Gln Glu Glu Thr Trp Arg Leu Ser Phe Ser His Ile Glu Lys 370 375 380 Glu Ile Leu Asn Asn His Gly Lys Ser Lys Thr Cys Cys Glu Asn Lys 385 390 395 400 Glu Glu Lys Cys Cys Arg Lys Asp Cys Leu Lys Leu Met Lys Tyr Leu 405 410 415 Leu Glu Gln Leu Lys Glu Arg Phe Lys Asp Lys Lys His Leu Asp Lys 420 425 430 Phe Ser Ser Tyr His Val Lys Thr Ala Phe Phe His Val Cys Thr Gln 435 440 445 Asn Pro Gln Asp Ser Gln Trp Asp Arg Lys Asp Leu Gly Leu Cys Phe 450 455 460 Asp Asn Cys Val Thr Tyr Phe Leu Gln Cys Leu Arg Thr Glu Lys Leu 465 470 475 480 Glu Asn Tyr Phe Ile Pro Glu Phe Asn Leu Phe Ser Ser Asn Leu Ile 485 490 495 Asp Lys Arg Ser Lys Glu Phe Leu Thr Lys Gln Ile Glu Tyr Glu Arg 500 505 510 Asn Asn Glu Phe Pro Val Phe Asp Glu Phe 515 520 <210> SEQ ID NO 1255 <211> LENGTH: 1569 <212> TYPE: DNA

<213> ORGANISM: Homo sapiens <400> SEQUENCE: 1255 atgcaaccat ggcatggtaa ggcaatgcaa cgtgcatctg aggctggagc taccgcgccc 60 aaagcttcag cacggaacgc gcgcggtgct ccgatggatc cgacggagag ccctgctgca 120 ccggaagccg ctctgccaaa agcgggtaaa ttcgggccgg cgcggaaatc aggctcacgc 180 cagaaaaaga gtgctccgga tacacaggaa cgtccgcctg taagagctac cggcgcgcgc 240 gctaaaaaag cccctcagcg tgcgcaggat acccaaccat cggatgcaac gagcgcaccg 300 ggggcggagg gccttgagcc tcctgctgcg cgtgagccgg ccctctctcg cgcagggagt 360 tgccgccaac gaggcgcacg ctgctcgacg aaaccgcggc cccctccggg tccgtgggat 420 gttccatcgc caggcctgcc ggtttctgcg cctattctcg ttcgccgcga cgcggctcct 480 ggcgcttcga aactgagagc tgtcttagag aaactgaaac tctcgcggga tgatatatct 540 actgcggcag ggatggtcaa aggtgttgtg gatcatctcc tgttacgtct taagtgcgat 600 tcggccttcc gaggtgttgg ccttttaaac actgggtcat actatgagca cgttaagatc 660 agcgcgccga acgagttcga cgttatgttt aagcttgaag tccctcgcat acagctggaa 720 gaatactcca atacacgagc atattatttt gttaaattca aacgaaaccc caaagagaac 780 cctctttcac agtttctgga gggagaaatt ctgtctgcga gtaagatgct ctcgaagttc 840 cgaaaaatca ttaaagagga aatcaacgac atcaaagaca ctgatgttat catgaagagg 900 aaacgtgggg gctcaccggc ggtaacactg ctgatttcgg aaaagatctc agttgatatt 960 actttggcgc tcgaatcaaa atcatcgtgg ccggcgagta cacaggaagg gctccgtatt 1020 cagaattggc tgtctgcgaa agtccgcaaa caactgcgtt tgaaaccatt ttatttagtg 1080 ccaaaacacg cgaaagaagg caacggtttc caggaggaga cgtggcgact gtcatttagc 1140 cacatagaaa aggaaatatt aaataatcac gggaaaagta agacgtgctg cgagaataaa 1200 gaagagaagt gctgcaggaa agattgtctg aaactgatga aatacctgtt ggagcagctg 1260 aaagagaggt ttaaagataa gaagcatctg gacaaatttt cttcatatca cgttaaaacc 1320 gcattcttcc acgtatgcac acagaatccg caggactcac agtgggatcg gaaagatctg 1380 ggcctgtgct ttgacaactg cgtcacatat ttcttgcagt gcttgaggac tgaaaaattg 1440 gaaaactact tcattcccga gttcaattta ttcagtagta acctgatcga caagcgtagc 1500 aaagaattcc tgacgaagca gatcgaatac gaaagaaata acgaattccc ggtgtttgat 1560 gaattttaa 1569 <210> SEQ ID NO 1256 <400> SEQUENCE: 1256 000 <210> SEQ ID NO 1257 <211> LENGTH: 273 <212> TYPE: PRT <213> ORGANISM: Listeria monocytogenes <400> SEQUENCE: 1257 Met Asp Phe Ser Asn Met Ser Ile Leu His Tyr Leu Ala Asn Ile Val 1 5 10 15 Asp Ile Leu Val Val Trp Phe Val Ile Tyr Lys Val Ile Met Leu Ile 20 25 30 Arg Gly Thr Lys Ala Val Gln Leu Leu Lys Gly Ile Phe Ile Ile Ile 35 40 45 Ala Val Lys Leu Leu Ser Gly Phe Phe Gly Leu Gln Thr Val Glu Trp 50 55 60 Ile Thr Asp Gln Met Leu Thr Trp Gly Phe Leu Ala Ile Ile Ile Ile 65 70 75 80 Phe Gln Pro Glu Leu Arg Arg Ala Leu Glu Thr Leu Gly Arg Gly Asn 85 90 95 Ile Phe Thr Arg Tyr Gly Ser Arg Ile Glu Arg Glu Gln His His Leu 100 105 110 Ile Glu Ser Ile Glu Lys Ser Thr Gln Tyr Met Ala Lys Arg Arg Ile 115 120 125 Gly Ala Leu Ile Ser Val Ala Arg Asp Thr Gly Met Asp Asp Tyr Ile 130 135 140 Glu Thr Gly Ile Pro Leu Asn Ala Lys Ile Ser Ser Gln Leu Leu Ile 145 150 155 160 Asn Ile Phe Ile Pro Asn Thr Pro Leu His Asp Gly Ala Val Ile Ile 165 170 175 Lys Gly Asn Glu Ile Ala Ser Ala Ala Ser Tyr Leu Pro Leu Ser Asp 180 185 190 Ser Pro Phe Leu Ser Lys Glu Leu Gly Thr Arg His Arg Ala Ala Leu 195 200 205 Gly Ile Ser Glu Val Thr Asp Ser Ile Thr Ile Val Val Ser Glu Glu 210 215 220 Thr Gly Gly Ile Ser Leu Thr Lys Gly Gly Glu Leu Phe Arg Asp Val 225 230 235 240 Ser Glu Glu Glu Leu His Lys Ile Leu Leu Lys Glu Leu Val Thr Val 245 250 255 Thr Ala Lys Lys Pro Ser Ile Phe Ser Lys Trp Lys Gly Gly Lys Ser 260 265 270 Glu <210> SEQ ID NO 1258 <211> LENGTH: 822 <212> TYPE: DNA <213> ORGANISM: Listeria monocytogenes <400> SEQUENCE: 1258 atggactttt ccaacatgag tatccttcac tatttagcga atattgtaga cattttggtg 60 gtttggttcg taatttacaa ggttatcatg cttatccgcg gcacgaaagc cgtccagctg 120 ttgaagggga ttttcattat tattgccgtc aagttactta gcggcttctt cggattgcag 180 acagtggaat ggattactga tcaaatgctg acttggggtt tcttagccat tatcattatc 240 tttcaaccgg aattgcgtcg tgccctggag actttggggc gtggcaatat ctttacccgc 300 tatggatcac gcattgagcg tgaacaacac caccttattg agtctattga aaagtccacg 360 caatacatgg cgaagcgtcg cattggagct ttgatctctg tggctcgtga tacaggcatg 420 gacgactaca tcgagactgg cattccgctt aatgcgaaaa tctcatcgca attattgatt 480 aatatcttca tccccaatac ccctcttcac gatggcgcag tgatcattaa aggtaacgag 540 atcgcgagcg ctgccagtta tctgccattg tccgactcgc cgtttctttc taaggagctg 600 ggaactcgcc atcgtgccgc attagggatt tccgaggtga cagattcaat cacaatcgtt 660 gtcagcgagg aaacaggtgg gatttccctt acgaagggag gcgaactgtt ccgtgatgta 720 tccgaagaag aattgcataa gattttgctt aaagagctgg tgactgtcac agctaaaaaa 780 ccaagcattt tctccaaatg gaaaggaggt aagtccgagt ga 822 <210> SEQ ID NO 1259 <400> SEQUENCE: 1259 000 <210> SEQ ID NO 1260 <211> LENGTH: 403 <212> TYPE: PRT <213> ORGANISM: Kingella denitrificans <400> SEQUENCE: 1260 Met Ser Asp Tyr Thr Asn Asn Leu His Arg Val Phe Val Asp Gln Lys 1 5 10 15 Ile Gly Phe Lys Lys Lys Ile Thr Pro Thr Glu Gln Asp Leu Asn Phe 20 25 30 Phe Asn Gln Val Lys Lys Asp Val Lys Ser His Leu Lys Thr Lys Ile 35 40 45 Lys Glu Phe Leu Glu Gln Gln Gly Ile Ala Asn Ile Ala Pro Lys Phe 50 55 60 Arg Ile Gln Gly Ser Trp Ala Tyr Gly Thr Cys Asn Leu Pro Ala Lys 65 70 75 80 Gln Asp Gln Glu Met Asp Phe Asp Tyr Gly Val Tyr Leu Pro Val Arg 85 90 95 Ala Phe Glu Gly Phe Asn Pro Asp Ala Gly Ala Ser Glu Gln Ala Gln 100 105 110 Asn Tyr Phe Glu Gln Val Glu Leu Met Val Glu Asp Leu Cys His Gln 115 120 125 His Lys Trp Gln Leu Asp Thr Ser Ala Pro Ser Ser Cys Ile Arg Ile 130 135 140 Lys Ile Arg Ser Asn Ala His Met Asp Ile Pro Leu Tyr Ala Val Pro 145 150 155 160 Asp Asp Met Phe Asp Ser Leu Glu Glu Arg Asn Glu Leu Gln Val Ser 165 170 175 Leu Gly Thr Thr Thr Ala Ile Asp Lys Ser Leu Asn Tyr Ser Glu Trp 180 185 190 Ala Leu Glu Asp Phe Asn Ile Arg Ser Phe Ala Glu Glu Ser Leu Met 195 200 205 Asp Lys Asn Ile Arg Met Ile His Met Ala Arg Arg Asp Gly Thr Trp 210 215 220 Gln Lys Ser Asp Cys Glu Leu Ile Arg Lys Trp Phe Ala Asp Lys Leu 225 230 235 240 Lys Ser Leu Glu Asn Asn Gly Gln Gln Leu Arg Ala Ile Cys Arg Tyr 245 250 255 Leu Lys Ala Trp Arg Asp Trp Gln Phe Ala Asp Lys Ser Phe Gln Pro 260 265 270 Ser Ser Ile Leu Leu Met Ile Ile Ala Cys Lys Tyr Tyr Gln Tyr His 275 280 285 Gln His Arg Asp Asp Leu Ala Leu Leu Ser Val Leu Glu Lys Leu Pro 290 295 300 Asn Ala Leu Asn Asp Asn Val Tyr Glu Asn Ile Glu Glu His Glu Ser 305 310 315 320 Glu Asp Phe Asn Arg Met Glu Glu Tyr Glu Arg Val Glu Ala Ser Gln 325 330 335 Tyr Ala Asp Ala Leu Tyr Gln Ser Phe Met Ala Ser Leu Asn Asn Leu 340 345 350 Asp Lys Thr Lys Val Leu Asn Phe Ile Thr Asn Glu Trp Gly Asp Arg 355 360 365 Ile Pro Gln Asp Glu Asn Leu Ile Glu Thr Ser Pro Gln Ser Ile Phe 370 375 380 Asp Thr Pro Pro Leu Ala Gln Ser Asn Ile Thr Gln Gln Val Pro Leu 385 390 395 400

Arg Gln Gly <210> SEQ ID NO 1261 <211> LENGTH: 403 <212> TYPE: PRT <213> ORGANISM: Neisseria bacilliformis <400> SEQUENCE: 1261 Met Ser His Tyr Thr Asn Asn Leu His Arg Ile Phe Val Asp Arg Glu 1 5 10 15 Ile Gly Phe Lys Lys Glu Ile Thr Pro Thr Glu Leu Asp Leu Asp Phe 20 25 30 Phe Asn Asn Val Lys Lys Val Val Lys Ser His Leu Lys Thr Lys Ile 35 40 45 Lys Glu Phe Leu Glu Gln Gln Gly Leu Ala Ser Ile Thr Pro Lys Phe 50 55 60 Arg Ile Gln Gly Ser Trp Ala Tyr Gly Thr Cys Asn Leu Pro Ala Lys 65 70 75 80 Gln Gly Gln Glu Met Asp Phe Asp Tyr Gly Val Tyr Leu Pro Val Arg 85 90 95 Ala Phe Asp Gly Phe Asn Pro Asp Ala Gly Ala Ser Glu Gln Ala Lys 100 105 110 Asn Tyr Phe Glu Gln Val Glu Leu Met Met Gly Asp Leu Cys Glu Gln 115 120 125 His Asp Trp Leu Leu Asp Thr Ser Ala Pro Ser Ser Cys Ile Arg Ile 130 135 140 Lys Ile Arg Asn Asn Ala His Met Asp Ile Pro Leu Tyr Ala Val Pro 145 150 155 160 Asp Asp Met Phe Asp Ser Leu Glu Glu Arg Asn Glu Leu Gln Val Ser 165 170 175 Leu Gly Ser Ala Thr Ala Ile His Glu Ser Leu Asn Tyr Ser Lys Trp 180 185 190 Val Phe Glu Asp Phe Asn Ile Arg Ser Phe Ala Glu Glu Ser Leu Met 195 200 205 Asp Lys Asn Ile Arg Met Ile His Met Ala Arg Arg Asp Gly Thr Trp 210 215 220 Gln Glu Ser Asp Cys Glu Leu Ile Arg Lys Trp Phe Ala Asp Lys Leu 225 230 235 240 Lys Ser Leu Glu Asn Asn Gly Gln Gln Leu Arg Ala Ile Cys Arg Tyr 245 250 255 Leu Lys Ala Trp Arg Asp Trp Gln Phe Ala Asp Lys Ser Phe Gln Pro 260 265 270 Ser Ser Ile Leu Leu Met Ile Ile Ala Cys Lys Tyr Tyr Gln Tyr Tyr 275 280 285 Gln His Arg Asp Asp Leu Ala Leu Leu Ser Val Leu Glu Lys Leu Pro 290 295 300 Asn Ala Leu Ser Gly Asn Val Tyr Glu Asn Ile Glu Glu His Glu Ser 305 310 315 320 Glu Asp Phe Asn Arg Met Lys Glu Gly Glu Arg Val Glu Ala Met Gln 325 330 335 Tyr Ala Asp Ala Leu Tyr Gln Asn Phe Met Ala Ser Leu Asn Asn Phe 340 345 350 Asp Lys Thr Lys Ala Leu Lys Phe Ile Thr Asn Glu Trp Gly Asn Arg 355 360 365 Ile Pro Gln Asp Glu Asp Leu Ile Glu Thr Ser Arg Gln Ala Ile Phe 370 375 380 Asp Thr Pro Pro Leu Val Gln Pro Asn Ile Thr Pro Gln Ala Pro Leu 385 390 395 400 Arg Gln Gly <210> SEQ ID NO 1262 <211> LENGTH: 468 <212> TYPE: PRT <213> ORGANISM: Verminephrobacter eiseniae <400> SEQUENCE: 1262 Met Gly Gln Ala Ser Lys Leu Phe Asn Gly Asn Thr Asp Gln Thr Leu 1 5 10 15 Ile Gly Arg Val Thr Pro Thr Thr Glu Gln Arg Glu Phe Leu Gln Gln 20 25 30 Gln Trp Asn Asp Leu Ala Asp His Leu Lys Gln Ala Leu Ala Lys His 35 40 45 Gly Tyr Thr Ile Ser Thr Trp Leu Gln Gly Ser Tyr Lys Tyr Ala Thr 50 55 60 Leu Ile Lys Pro Val His Leu Gly Glu Glu Tyr Asp Val Asp Val Gly 65 70 75 80 Leu Tyr Phe Glu Trp Asn Asp Asp Gln Asp Ala Glu Pro Thr Pro Lys 85 90 95 Gln Leu Arg Asp Trp Val Gln Ala Glu Leu Leu Glu Tyr Glu Lys Ala 100 105 110 Cys Glu Glu Leu Lys Lys Val Glu Val Pro Pro Lys Glu Arg Cys Ser 115 120 125 Arg Ala Ser Tyr Ile Gln Gln Phe His Ile Asp Thr Pro Val Tyr His 130 135 140 Leu Asn Thr Asp Ser Asp Val Arg Arg Leu Ala Cys Leu Ser Gly Lys 145 150 155 160 Trp Glu His Ser Asp Pro Lys Lys Leu Tyr Lys Trp Phe Lys Glu Ala 165 170 175 Val Ser Gly Asp Asp Arg Asp Gln Leu Arg Arg Leu Val Arg Tyr Leu 180 185 190 Lys Ala Trp Ala Ala Val Ser Phe Asp Asp Ala Pro Gly Ser Arg Pro 195 200 205 Ser Ser Ile Phe Leu Thr Val Ile Ala Thr Glu Ala Tyr Gln Asp Leu 210 215 220 Trp Ala Gln Arg Leu Leu Gly Leu Ala Asp Asp Asp Ala Leu Leu Ala 225 230 235 240 Val Ile Lys Lys Met His Asp Arg Leu Phe Asp Asp Arg Lys Val Glu 245 250 255 Asn Pro Val Asp Lys Asn Glu Asp Leu Asn Arg Met Thr Ala Glu Ala 260 265 270 Trp Asp Gly Phe Leu Pro Arg Leu Ala Ala Leu Gln Asp Ile Ala Glu 275 280 285 Arg Ala Gly Asp Ala Lys Asp Glu Ala Ser Ala Ala Leu Ile Trp Ser 290 295 300 Glu Ala Phe Ser Phe Leu Met Pro Leu Pro Glu Thr Asp Gln Val Glu 305 310 315 320 Ile Val Asp Glu Gly Ser Gly Arg Ala Val Met Gln Leu Pro Glu Ile 325 330 335 Glu Val Lys Val Cys Thr Gly Thr Pro Pro Arg Pro Val Ala Thr Tyr 340 345 350 Arg Asn Glu Val Pro Gly Val Ala Lys Asp Cys Met Leu Ser Phe Ala 355 360 365 Ile Val Asn Pro His Val Val Pro Glu Phe Ala Thr Val Glu Trp Thr 370 375 380 Val Arg Asn Glu Gly Gln Glu Ala Asp Gln Arg Ser Asp Leu Gly His 385 390 395 400 Arg Arg Val Gly Met Arg Leu Leu Ser Val Glu Glu His Thr Ala Tyr 405 410 415 Val Gly Arg His Phe Met Asp Cys Val Val Arg Leu Asn Gly Gln Val 420 425 430 Tyr Ala Val Arg Arg Val Pro Val Thr Ile Arg Asp Val Gln His Val 435 440 445 Ala Arg Asn Pro Pro Arg Pro Pro Tyr Thr Lys Leu Arg Ser Leu Phe 450 455 460 Arg Arg Arg Arg 465 <210> SEQ ID NO 1263 <211> LENGTH: 1213 <212> TYPE: DNA <213> ORGANISM: Kingella denitrificans <400> SEQUENCE: 1263 atgtcagact acactaataa cttgcatcgc gtctttgttg accaaaaaat tgggttcaag 60 aagaaaatca ctcctaccga gcaagatctg aactttttca atcaggtcaa gaaagatgta 120 aagtcccacc ttaagaccaa aatcaaggaa tttcttgagc aacagggaat cgcgaacatt 180 gctccgaagt tccgtattca gggatcgtgg gcttacggga catgtaattt gcccgcaaaa 240 caggaccagg agatggattt cgattacggg gtatatctgc cagtacgtgc cttcgagggg 300 ttcaacccag acgcaggcgc gtctgagcag gctcaaaact attttgaaca ggtcgagttg 360 atggttgaag atctgtgcca ccagcataaa tggcagctgg acacgtctgc cccttcgtcc 420 tgtatccgca ttaaaattcg cagcaacgct catatggaca ttcctttata tgccgtcccg 480 gatgatatgt tcgattctct tgaagagcgc aatgagttac aagtatcact gggcacgaca 540 acggctatcg ataagtcact gaattacagc gagtgggcac tggaggactt taatatccgc 600 tcattcgccg aagaaagttt aatggataag aacattcgca tgatccacat ggcgcgtcgt 660 gacgggactt ggcaaaagtc ggattgcgag ctgattcgca aatggttcgc agacaaactg 720 aagagcttgg agaataacgg gcaacagctg cgtgcgatct gtcgttacct taaggcgtgg 780 cgcgattggc aattcgctga caagtcgttt caaccatcct ctatcttgtt aatgattatc 840 gcgtgcaaat attatcaata ccatcaacac cgtgacgatt tagcactttt atccgtgctt 900 gaaaagttgc caaacgcttt aaacgataat gtttatgaga atattgaaga acacgaatcc 960 gaagacttta accgtatgga agagtatgaa cgcgttgagg cgtcgcagta tgccgacgcg 1020 ttgtaccaga gtttcatggc ctccttaaac aatttggaca aaactaaggt tttaaatttt 1080 atcactaatg agtgggggga tcgcattcca caagacgaga acttaatcga gacatctcct 1140 caatcaattt tcgatactcc ccccttggca caaagcaata tcacgcaaca agtgcccttg 1200 cgccagggtt aas 1213 <210> SEQ ID NO 1264 <211> LENGTH: 1212 <212> TYPE: DNA <213> ORGANISM: Neisseria bacilliformis <400> SEQUENCE: 1264 atgtctcact acaccaataa tcttcatcgt atcttcgtag atcgtgaaat tggttttaag 60 aaagagatta ctccgacaga gctggatctt gacttcttca acaacgtcaa aaaagtagtt 120 aagagccacc ttaaaaccaa aatcaaggag tttcttgaac agcaagggct ggcgagtatt 180 actcctaagt ttcgtatcca gggaagctgg gcgtacggaa catgtaacct tccagccaag 240

cagggtcagg aaatggactt cgattatggc gtttatcttc ctgtccgcgc ctttgatgga 300 tttaatcctg atgcaggtgc ctcagaacaa gctaagaatt acttcgaaca ggtggagctt 360 atgatgggtg acctgtgcga gcagcatgac tggttgttgg acacatccgc gccctcttcg 420 tgtattcgca tcaaaatccg caataatgcc catatggaca ttcctttata tgcagttcca 480 gacgatatgt tcgatagcct ggaggaacgt aacgaattac aggtttcctt gggatcagcg 540 acagctattc acgaatcgct gaattattca aagtgggttt ttgaggattt taacatccgc 600 tcttttgctg aggaatccct gatggacaaa aatatccgca tgatccacat ggcccgccgt 660 gacggaactt ggcaggagtc tgattgtgag ttgattcgca aatggtttgc tgacaagttg 720 aaatcccttg agaataatgg tcagcagctt cgtgcaattt gtcgctatct taaagcctgg 780 cgcgattggc aattcgcaga taagtctttt caaccctcca gtatcctgtt gatgatcatt 840 gcgtgtaagt actatcagta ctaccaacat cgtgacgacc tggcactgct gtccgtgctg 900 gagaaattgc ccaacgcttt gtctgggaac gtctatgaga atattgagga acatgagtct 960 gaggacttta accgtatgaa agagggcgag cgtgtagaag caatgcaata tgcggacgcg 1020 ttataccaaa acttcatggc gtctcttaac aattttgata aaacgaaggc gctgaaattc 1080 atcactaatg aatggggaaa tcgtatccca caagatgaag acttaatcga aacgtctcgt 1140 caggcaattt ttgacacacc acccttagtt caacccaaca tcactccaca ggccccactt 1200 cgccaggggt aa 1212 <210> SEQ ID NO 1265 <211> LENGTH: 1407 <212> TYPE: DNA <213> ORGANISM: Verminephrobacter eiseniae <400> SEQUENCE: 1265 atgggacagg cgtctaagtt atttaatggt aatacagatc aaactttaat tggccgcgtg 60 acgcccacta ccgaacaacg cgagttttta caacagcagt ggaatgatct ggcagatcac 120 ttgaagcaag ccctggcaaa acacggttat acaatttcga catggcttca gggttcttac 180 aaatacgcga ctcttattaa gcctgtgcat ctgggtgaag agtatgacgt agatgtaggg 240 ttgtactttg agtggaacga tgaccaggat gcggagccca cgcctaagca gctgcgtgat 300 tgggtgcaag cggagttgtt agagtatgag aaggcttgtg aggaacttaa gaaagttgag 360 gtgccgccga aagaacgctg ttctcgcgca tcatacatcc aacaatttca cattgacaca 420 ccagtttatc atctgaacac ggactccgac gtgcgccgtc ttgcttgcct tagtggaaag 480 tgggagcatt ctgatccgaa aaagttatac aagtggttta aagaagcagt atccggggat 540 gatcgtgacc aattacgccg tcttgtacgt tacttaaagg cctgggctgc ggtttccttt 600 gatgacgcac cgggatcccg cccatctagc atttttctta cggttattgc tactgaagcc 660 tatcaggact tgtgggcaca acgtttactg ggattagctg acgatgacgc tttgctggca 720 gtgattaaaa agatgcacga ccgccttttc gatgaccgca aggtcgagaa tcccgtagat 780 aaaaacgaag acttaaatcg catgacggct gaagcgtggg acggttttct gccccgcttg 840 gcggcacttc aagacattgc ggaacgcgcc ggagatgcta aggatgaggc gtcagccgca 900 ttgatctgga gcgaagcgtt tagttttttg atgcccttgc cggaaactga tcaggtagaa 960 atcgtagacg aaggctcagg ccgtgccgtc atgcaattgc cagaaattga ggtaaaggtc 1020 tgcactggca cgccaccccg cccagtcgca acgtatcgta atgaggtccc aggagtagca 1080 aaagactgca tgttgtcctt tgcgattgtc aatccacatg tggttccgga gtttgccacg 1140 gtggagtgga ctgtgcgtaa tgagggacag gaggcggacc agcgtagtga tttagggcac 1200 cgtcgcgtcg ggatgcgttt gttgagtgta gaggaacata cggcatatgt cggtcgtcac 1260 tttatggatt gtgtagtccg tctgaacggg caagtttacg ctgtccgtcg cgtacccgtt 1320 accattcgcg acgttcagca cgtcgcccgc aatcccccac gtccacctta cacaaaactg 1380 cgcagtttat tccgccgccg tcgctaa 1407 <210> SEQ ID NO 1266 <400> SEQUENCE: 1266 000 <210> SEQ ID NO 1267 <400> SEQUENCE: 1267 000 <210> SEQ ID NO 1268 <211> LENGTH: 621 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1268 ctaacgtttg aattttgcgt aacgttcgcg agcaatctct aaagtgctat tacgtacacg 60 ctcaaaacgt tccttatcct tctgccataa cgaacgcacc gcaagaccac gcacgctgtt 120 aaaaatcaac cacaaaatgt cctcggcatc gtcacgggat aatccacgcg acaccagaac 180 gcccaaccac atatcctcga ccacaaaacg gttgcgctct accgtgcgtt ggataccctc 240 acgcagagct ggatcacgat cagcggccac aatcagatca aggctaattg aaaagtcgtc 300 atccaagaaa aactcagcgg catcatcaag catttgctga atcacatcat cttccggttt 360 taacttagcc aggcgagcac ggctgcgctc ggtgatctgc tcatacagcc actcaaacgt 420 agcaagcaac agttctaatt tggtgggaaa atggtgtgac tgggcgccac gagacacccc 480 cgcggcgccc ggtacatccg caatacgaaa acccgcgtat cccttctcgc gtaatacacc 540 aagcgccgcc gcgatcagtt taccttgtgt ttccatcgca cgttcggctt gagtacggcg 600 cttgggcgac atgattacca t 621 <210> SEQ ID NO 1269 <211> LENGTH: 206 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1269 Met Val Ile Met Ser Pro Lys Arg Arg Thr Gln Ala Glu Arg Ala Met 1 5 10 15 Glu Thr Gln Gly Lys Leu Ile Ala Ala Ala Leu Gly Val Leu Arg Glu 20 25 30 Lys Gly Tyr Ala Gly Phe Arg Ile Ala Asp Val Pro Gly Ala Ala Gly 35 40 45 Val Ser Arg Gly Ala Gln Ser His His Phe Pro Thr Lys Leu Glu Leu 50 55 60 Leu Leu Ala Thr Phe Glu Trp Leu Tyr Glu Gln Ile Thr Glu Arg Ser 65 70 75 80 Arg Ala Arg Leu Ala Lys Leu Lys Pro Glu Asp Asp Val Ile Gln Gln 85 90 95 Met Leu Asp Asp Ala Ala Glu Phe Phe Leu Asp Asp Asp Phe Ser Ile 100 105 110 Ser Leu Asp Leu Ile Val Ala Ala Asp Arg Asp Pro Ala Leu Arg Glu 115 120 125 Gly Ile Gln Arg Thr Val Glu Arg Asn Arg Phe Val Val Glu Asp Met 130 135 140 Trp Leu Gly Val Leu Val Ser Arg Gly Leu Ser Arg Asp Asp Ala Glu 145 150 155 160 Asp Ile Leu Trp Leu Ile Phe Asn Ser Val Arg Gly Leu Ala Val Arg 165 170 175 Ser Leu Trp Gln Lys Asp Lys Glu Arg Phe Glu Arg Val Arg Asn Ser 180 185 190 Thr Leu Glu Ile Ala Arg Glu Arg Tyr Ala Lys Phe Lys Arg 195 200 205 <210> SEQ ID NO 1270 <211> LENGTH: 123 <212> TYPE: DNA <213> ORGANISM: Escherichia coli <400> SEQUENCE: 1270 taacaccgtg cgtgttgact attttacctc tggcggtgat aatggttgca acaaacagac 60 aatctggtct gtttgtatta tgttaaccag cacactggcg gccgcttact agaaataatt 120 ttg 123 <210> SEQ ID NO 1271 <211> LENGTH: 161 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1271 taacaccgtg cgtgttgact attttacctc tggcggtgat aatggttgca acaaacagac 60 aatctggtct gtttgtatta tgttaaccag cacactggcg gccgcttact agaaataatt 120 ttggccgcat cccacgctaa ctaatataaa ggaggtttta a 161 <210> SEQ ID NO 1272 <400> SEQUENCE: 1272 000 <210> SEQ ID NO 1273 <211> LENGTH: 79 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1273 tgtatttatc aatattgttt gctccgttat cgttattaac aagtcatcaa taaagccatc 60 acgagtacca tagaggatc 79 <210> SEQ ID NO 1274 <211> LENGTH: 117 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE:

<223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1274 tgtatttatc aatattgttt gctccgttat cgttattaac aagtcatcaa taaagccatc 60 acgagtacca tagaggatcg ccgcatccca cgctaactaa tataaaggag gttttaa 117 <210> SEQ ID NO 1275 <400> SEQUENCE: 1275 000 <210> SEQ ID NO 1276 <400> SEQUENCE: 1276 000 <210> SEQ ID NO 1277 <400> SEQUENCE: 1277 000 <210> SEQ ID NO 1278 <211> LENGTH: 903 <212> TYPE: DNA <213> ORGANISM: Pseudomonas sp. <400> SEQUENCE: 1278 tcaatctgta aacaaatcga acatcagttg acgaagccag atattggcca aatccttatg 60 gtatttagcg tgccagaaca tattaatggc aatctcggga agcactaccg gatgaggcag 120 agcggacaag ccgaaaggtt cgacacagca atccgctaag cggatcggca ctgttgccag 180 caggtcagta cgttgaagaa tatggccaac ggctgcgaaa tggggcactt ccagacgaat 240 atcacgacgg atgcctacac gggtcatata cgtgtccact tcaccgtggc ctgtgcctgc 300 tgcaataaca cgtacatgtc cataactaca aaagcgttca agcgtcaatg gctcacgggt 360 aacggggtgg tccttgcggc acaaacaaac gtagtggttt tgcagtaaac ggcgttggaa 420 gaagcctgtt tgaaggttgg gcagaagccc caccgccaaa tcgacagttc cattttgcaa 480 cgcctgcatt aatgacatag acgaatcgcg gacagtagaa atgacgcagt tcggtgcttg 540 atgggcaagt acgtccatca ggcgaggcat gaaataaatc tccccaatat ccgtcattgc 600 cagggtgaaa gtacgctccg aagtaagggg gtcaaagctc tcatgatgtt gtaaagcgtt 660 acgaagggcg tgcatggcac tggtgacagg ctcggccaag tgtgcggcgt atggcgttgg 720 ttccatccct tggtgagtac ggacgaacaa cggatcttgt aacgatgtac gaaggcgttt 780 taatgcgtta gaaactgcgg gttgagtaag cccaagattt tctgcggtga tggagacgcg 840 acgatctacc agcagctgat taaagacaac taacaggtta aggtccagat cacgcaattc 900 cat 903 <210> SEQ ID NO 1279 <400> SEQUENCE: 1279 000 <210> SEQ ID NO 1280 <211> LENGTH: 300 <212> TYPE: PRT <213> ORGANISM: Pseudomonas sp. <400> SEQUENCE: 1280 Met Glu Leu Arg Asp Leu Asp Leu Asn Leu Leu Val Val Phe Asn Gln 1 5 10 15 Leu Leu Val Asp Arg Arg Val Ser Ile Thr Ala Glu Asn Leu Gly Leu 20 25 30 Thr Gln Pro Ala Val Ser Asn Ala Leu Lys Arg Leu Arg Thr Ser Leu 35 40 45 Gln Asp Pro Leu Phe Val Arg Thr His Gln Gly Met Glu Pro Thr Pro 50 55 60 Tyr Ala Ala His Leu Ala Glu Pro Val Thr Ser Ala Met His Ala Leu 65 70 75 80 Arg Asn Ala Leu Gln His His Glu Ser Phe Asp Pro Leu Thr Ser Glu 85 90 95 Arg Thr Phe Thr Leu Ala Met Thr Asp Ile Gly Glu Ile Tyr Phe Met 100 105 110 Pro Arg Leu Met Asp Val Leu Ala His Gln Ala Pro Asn Cys Val Ile 115 120 125 Ser Thr Val Arg Asp Ser Ser Met Ser Leu Met Gln Ala Leu Gln Asn 130 135 140 Gly Thr Val Asp Leu Ala Val Gly Leu Leu Pro Asn Leu Gln Thr Gly 145 150 155 160 Phe Phe Gln Arg Arg Leu Leu Gln Asn His Tyr Val Cys Leu Cys Arg 165 170 175 Lys Asp His Pro Val Thr Arg Glu Pro Leu Thr Leu Glu Arg Phe Cys 180 185 190 Ser Tyr Gly His Val Arg Val Ile Ala Ala Gly Thr Gly His Gly Glu 195 200 205 Val Asp Thr Tyr Met Thr Arg Val Gly Ile Arg Arg Asp Ile Arg Leu 210 215 220 Glu Val Pro His Phe Ala Ala Val Gly His Ile Leu Gln Arg Thr Asp 225 230 235 240 Leu Leu Ala Thr Val Pro Ile Arg Leu Ala Asp Cys Cys Val Glu Pro 245 250 255 Phe Gly Leu Ser Ala Leu Pro His Pro Val Val Leu Pro Glu Ile Ala 260 265 270 Ile Asn Met Phe Trp His Ala Lys Tyr His Lys Asp Leu Ala Asn Ile 275 280 285 Trp Leu Arg Gln Leu Met Phe Asp Leu Phe Thr Asp 290 295 300 <210> SEQ ID NO 1281 <211> LENGTH: 164 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1281 agttgttctt attggtggtg ttgctttatg gttgcatcgt agtaaatggt tgtaacaaaa 60 gcaatttttc cggctgtctg tatacaaaaa cgccgcaaag tttgagcgaa gtcaataaac 120 tctctaccca ttcagggcaa tatctctctt ggatccaaag tgaa 164 <210> SEQ ID NO 1282 <211> LENGTH: 201 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1282 agttgttctt attggtggtg ttgctttatg gttgcatcgt agtaaatggt tgtaacaaaa 60 gcaatttttc cggctgtctg tatacaaaaa cgccgcaaag tttgagcgaa gtcaataaac 120 tctctaccca ttcagggcaa tatctctctt ggatccaaag tgaacccgca tcccacgcta 180 actaatataa ggggggcaag a 201 <210> SEQ ID NO 1283 <400> SEQUENCE: 1283 000 <210> SEQ ID NO 1284 <211> LENGTH: 1023 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1284 agttgttctt attggtggtg ttgctttatg gttgcatcgt agtaaatggt tgtaacaaaa 60 gcaatttttc cggctgtctg tatacaaaaa cgccgcaaag tttgagcgaa gtcaataaac 120 tctctaccca ttcagggcaa tatctctctt ggatccaaag tgaacccgca tcccacgcta 180 actaatataa ggggggcaag aatggacttt tccaacatga gtatccttca ctatttagcg 240 aatattgtag acattttggt ggtttggttc gtaatttaca aggttatcat gcttatccgc 300 ggcacgaaag ccgtccagct gttgaagggg attttcatta ttattgccgt caagttactt 360 agcggcttct tcggattgca gacagtggaa tggattactg atcaaatgct gacttggggt 420 ttcttagcca ttatcattat ctttcaaccg gaattgcgtc gtgccctgga gactttgggg 480 cgtggcaata tctttacccg ctatggatca cgcattgagc gtgaacaaca ccaccttatt 540 gagtctattg aaaagtccac gcaatacatg gcgaagcgtc gcattggagc tttgatctct 600 gtggctcgtg atacaggcat ggacgactac atcgagactg gcattccgct taatgcgaaa 660 atctcatcgc aattattgat taatatcttc atccccaata cccctcttca cgatggcgca 720 gtgatcatta aaggtaacga gatcgcgagc gctgccagtt atctgccatt gtccgactcg 780 ccgtttcttt ctaaggagct gggaactcgc catcgtgccg cattagggat ttccgaggtg 840 acagattcaa tcacaatcgt tgtcagcgag gaaacaggtg ggatttccct tacgaaggga 900 ggcgaactgt tccgtgatgt atccgaagaa gaattgcata agattttgct taaagagctg 960 gtgactgtca cagctaaaaa accaagcatt ttctccaaat ggaaaggagg taagtccgag 1020 tga 1023 <210> SEQ ID NO 1285 <400> SEQUENCE: 1285 000 <210> SEQ ID NO 1286 <400> SEQUENCE: 1286 000

<210> SEQ ID NO 1287 <400> SEQUENCE: 1287 000 <210> SEQ ID NO 1288 <400> SEQUENCE: 1288 000 <210> SEQ ID NO 1289 <400> SEQUENCE: 1289 000 <210> SEQ ID NO 1290 <400> SEQUENCE: 1290 000 <210> SEQ ID NO 1291 <400> SEQUENCE: 1291 000 <210> SEQ ID NO 1292 <400> SEQUENCE: 1292 000 <210> SEQ ID NO 1293 <400> SEQUENCE: 1293 000 <210> SEQ ID NO 1294 <400> SEQUENCE: 1294 000 <210> SEQ ID NO 1295 <400> SEQUENCE: 1295 000 <210> SEQ ID NO 1296 <400> SEQUENCE: 1296 000 <210> SEQ ID NO 1297 <400> SEQUENCE: 1297 000 <210> SEQ ID NO 1298 <400> SEQUENCE: 1298 000 <210> SEQ ID NO 1299 <400> SEQUENCE: 1299 000 <210> SEQ ID NO 1300 <400> SEQUENCE: 1300 000 <210> SEQ ID NO 1301 <400> SEQUENCE: 1301 000 <210> SEQ ID NO 1302 <400> SEQUENCE: 1302 000 <210> SEQ ID NO 1303 <400> SEQUENCE: 1303 000 <210> SEQ ID NO 1304 <400> SEQUENCE: 1304 000 <210> SEQ ID NO 1305 <400> SEQUENCE: 1305 000 <210> SEQ ID NO 1306 <400> SEQUENCE: 1306 000 <210> SEQ ID NO 1307 <400> SEQUENCE: 1307 000 <210> SEQ ID NO 1308 <400> SEQUENCE: 1308 000 <210> SEQ ID NO 1309 <400> SEQUENCE: 1309 000 <210> SEQ ID NO 1310 <400> SEQUENCE: 1310 000 <210> SEQ ID NO 1311 <400> SEQUENCE: 1311 000 <210> SEQ ID NO 1312 <400> SEQUENCE: 1312 000 <210> SEQ ID NO 1313 <400> SEQUENCE: 1313 000 <210> SEQ ID NO 1314 <400> SEQUENCE: 1314 000 <210> SEQ ID NO 1315 <400> SEQUENCE: 1315 000 <210> SEQ ID NO 1316 <400> SEQUENCE: 1316 000 <210> SEQ ID NO 1317 <400> SEQUENCE: 1317 000 <210> SEQ ID NO 1318 <400> SEQUENCE: 1318 000 <210> SEQ ID NO 1319 <400> SEQUENCE: 1319 000 <210> SEQ ID NO 1320 <400> SEQUENCE: 1320 000 <210> SEQ ID NO 1321 <400> SEQUENCE: 1321 000 <210> SEQ ID NO 1322 <400> SEQUENCE: 1322 000

<210> SEQ ID NO 1323 <400> SEQUENCE: 1323 000 <210> SEQ ID NO 1324 <400> SEQUENCE: 1324 000 <210> SEQ ID NO 1325 <400> SEQUENCE: 1325 000 <210> SEQ ID NO 1326 <400> SEQUENCE: 1326 000 <210> SEQ ID NO 1327 <400> SEQUENCE: 1327 000 <210> SEQ ID NO 1328 <400> SEQUENCE: 1328 000 <210> SEQ ID NO 1329 <400> SEQUENCE: 1329 000 <210> SEQ ID NO 1330 <400> SEQUENCE: 1330 000 <210> SEQ ID NO 1331 <400> SEQUENCE: 1331 000 <210> SEQ ID NO 1332 <400> SEQUENCE: 1332 000 <210> SEQ ID NO 1333 <400> SEQUENCE: 1333 000 <210> SEQ ID NO 1334 <400> SEQUENCE: 1334 000 <210> SEQ ID NO 1335 <400> SEQUENCE: 1335 000 <210> SEQ ID NO 1336 <400> SEQUENCE: 1336 000 <210> SEQ ID NO 1337 <400> SEQUENCE: 1337 000 <210> SEQ ID NO 1338 <400> SEQUENCE: 1338 000 <210> SEQ ID NO 1339 <400> SEQUENCE: 1339 000 <210> SEQ ID NO 1340 <400> SEQUENCE: 1340 000 <210> SEQ ID NO 1341 <400> SEQUENCE: 1341 000 <210> SEQ ID NO 1342 <400> SEQUENCE: 1342 000 <210> SEQ ID NO 1343 <400> SEQUENCE: 1343 000 <210> SEQ ID NO 1344 <400> SEQUENCE: 1344 000 <210> SEQ ID NO 1345 <400> SEQUENCE: 1345 000 <210> SEQ ID NO 1346 <400> SEQUENCE: 1346 000 <210> SEQ ID NO 1347 <400> SEQUENCE: 1347 000 <210> SEQ ID NO 1348 <400> SEQUENCE: 1348 000 <210> SEQ ID NO 1349 <400> SEQUENCE: 1349 000 <210> SEQ ID NO 1350 <400> SEQUENCE: 1350 000 <210> SEQ ID NO 1351 <400> SEQUENCE: 1351 000 <210> SEQ ID NO 1352 <400> SEQUENCE: 1352 000 <210> SEQ ID NO 1353 <400> SEQUENCE: 1353 000 <210> SEQ ID NO 1354 <400> SEQUENCE: 1354 000 <210> SEQ ID NO 1355 <400> SEQUENCE: 1355 000 <210> SEQ ID NO 1356 <400> SEQUENCE: 1356 000 <210> SEQ ID NO 1357 <400> SEQUENCE: 1357 000 <210> SEQ ID NO 1358 <400> SEQUENCE: 1358 000

<210> SEQ ID NO 1359 <400> SEQUENCE: 1359 000 <210> SEQ ID NO 1360 <400> SEQUENCE: 1360 000 <210> SEQ ID NO 1361 <400> SEQUENCE: 1361 000 <210> SEQ ID NO 1362 <400> SEQUENCE: 1362 000 <210> SEQ ID NO 1363 <400> SEQUENCE: 1363 000 <210> SEQ ID NO 1364 <400> SEQUENCE: 1364 000 <210> SEQ ID NO 1365 <400> SEQUENCE: 1365 000 <210> SEQ ID NO 1366 <400> SEQUENCE: 1366 000 <210> SEQ ID NO 1367 <400> SEQUENCE: 1367 000 <210> SEQ ID NO 1368 <400> SEQUENCE: 1368 000 <210> SEQ ID NO 1369 <400> SEQUENCE: 1369 000 <210> SEQ ID NO 1370 <400> SEQUENCE: 1370 000 <210> SEQ ID NO 1371 <400> SEQUENCE: 1371 000 <210> SEQ ID NO 1372 <400> SEQUENCE: 1372 000 <210> SEQ ID NO 1373 <400> SEQUENCE: 1373 000 <210> SEQ ID NO 1374 <400> SEQUENCE: 1374 000 <210> SEQ ID NO 1375 <400> SEQUENCE: 1375 000 <210> SEQ ID NO 1376 <400> SEQUENCE: 1376 000 <210> SEQ ID NO 1377 <400> SEQUENCE: 1377 000 <210> SEQ ID NO 1378 <400> SEQUENCE: 1378 000 <210> SEQ ID NO 1379 <400> SEQUENCE: 1379 000 <210> SEQ ID NO 1380 <400> SEQUENCE: 1380 000 <210> SEQ ID NO 1381 <400> SEQUENCE: 1381 000 <210> SEQ ID NO 1382 <400> SEQUENCE: 1382 000 <210> SEQ ID NO 1383 <400> SEQUENCE: 1383 000 <210> SEQ ID NO 1384 <400> SEQUENCE: 1384 000 <210> SEQ ID NO 1385 <400> SEQUENCE: 1385 000 <210> SEQ ID NO 1386 <400> SEQUENCE: 1386 000 <210> SEQ ID NO 1387 <400> SEQUENCE: 1387 000 <210> SEQ ID NO 1388 <400> SEQUENCE: 1388 000 <210> SEQ ID NO 1389 <400> SEQUENCE: 1389 000 <210> SEQ ID NO 1390 <400> SEQUENCE: 1390 000 <210> SEQ ID NO 1391 <400> SEQUENCE: 1391 000 <210> SEQ ID NO 1392 <400> SEQUENCE: 1392 000 <210> SEQ ID NO 1393 <400> SEQUENCE: 1393 000 <210> SEQ ID NO 1394 <400> SEQUENCE: 1394

000 <210> SEQ ID NO 1395 <400> SEQUENCE: 1395 000 <210> SEQ ID NO 1396 <400> SEQUENCE: 1396 000 <210> SEQ ID NO 1397 <400> SEQUENCE: 1397 000 <210> SEQ ID NO 1398 <400> SEQUENCE: 1398 000 <210> SEQ ID NO 1399 <400> SEQUENCE: 1399 000 <210> SEQ ID NO 1400 <400> SEQUENCE: 1400 000 <210> SEQ ID NO 1401 <400> SEQUENCE: 1401 000 <210> SEQ ID NO 1402 <400> SEQUENCE: 1402 000 <210> SEQ ID NO 1403 <400> SEQUENCE: 1403 000 <210> SEQ ID NO 1404 <400> SEQUENCE: 1404 000 <210> SEQ ID NO 1405 <400> SEQUENCE: 1405 000 <210> SEQ ID NO 1406 <400> SEQUENCE: 1406 000 <210> SEQ ID NO 1407 <400> SEQUENCE: 1407 000 <210> SEQ ID NO 1408 <400> SEQUENCE: 1408 000 <210> SEQ ID NO 1409 <400> SEQUENCE: 1409 000 <210> SEQ ID NO 1410 <400> SEQUENCE: 1410 000 <210> SEQ ID NO 1411 <400> SEQUENCE: 1411 000 <210> SEQ ID NO 1412 <400> SEQUENCE: 1412 000 <210> SEQ ID NO 1413 <400> SEQUENCE: 1413 000 <210> SEQ ID NO 1414 <400> SEQUENCE: 1414 000 <210> SEQ ID NO 1415 <400> SEQUENCE: 1415 000 <210> SEQ ID NO 1416 <400> SEQUENCE: 1416 000 <210> SEQ ID NO 1417 <400> SEQUENCE: 1417 000 <210> SEQ ID NO 1418 <400> SEQUENCE: 1418 000 <210> SEQ ID NO 1419 <400> SEQUENCE: 1419 000 <210> SEQ ID NO 1420 <400> SEQUENCE: 1420 000 <210> SEQ ID NO 1421 <400> SEQUENCE: 1421 000 <210> SEQ ID NO 1422 <400> SEQUENCE: 1422 000 <210> SEQ ID NO 1423 <400> SEQUENCE: 1423 000 <210> SEQ ID NO 1424 <400> SEQUENCE: 1424 000 <210> SEQ ID NO 1425 <400> SEQUENCE: 1425 000 <210> SEQ ID NO 1426 <400> SEQUENCE: 1426 000 <210> SEQ ID NO 1427 <400> SEQUENCE: 1427 000 <210> SEQ ID NO 1428 <400> SEQUENCE: 1428 000 <210> SEQ ID NO 1429 <400> SEQUENCE: 1429 000 <210> SEQ ID NO 1430 <400> SEQUENCE: 1430

000 <210> SEQ ID NO 1431 <400> SEQUENCE: 1431 000 <210> SEQ ID NO 1432 <400> SEQUENCE: 1432 000 <210> SEQ ID NO 1433 <400> SEQUENCE: 1433 000 <210> SEQ ID NO 1434 <400> SEQUENCE: 1434 000 <210> SEQ ID NO 1435 <400> SEQUENCE: 1435 000 <210> SEQ ID NO 1436 <400> SEQUENCE: 1436 000 <210> SEQ ID NO 1437 <400> SEQUENCE: 1437 000 <210> SEQ ID NO 1438 <400> SEQUENCE: 1438 000 <210> SEQ ID NO 1439 <400> SEQUENCE: 1439 000 <210> SEQ ID NO 1440 <400> SEQUENCE: 1440 000 <210> SEQ ID NO 1441 <400> SEQUENCE: 1441 000 <210> SEQ ID NO 1442 <400> SEQUENCE: 1442 000 <210> SEQ ID NO 1443 <211> LENGTH: 42 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1443 tcgacattta tcccttgcgg cgaatactta cagccatagc aa 42 <210> SEQ ID NO 1444 <211> LENGTH: 49 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1444 ggcgcgcctt gacaattaat catccggctc ctaggatgtg tggagggac 49 <210> SEQ ID NO 1445 <211> LENGTH: 50 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1445 ggcgcgcctt gacatcagga aaatttttct gtataataga ttcatctcaa 50 <210> SEQ ID NO 1446 <211> LENGTH: 51 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1446 ggcgcgcctt gacataaagt ctaacctata ggatacttac agccatacaa g 51 <210> SEQ ID NO 1447 <400> SEQUENCE: 1447 000 <210> SEQ ID NO 1448 <400> SEQUENCE: 1448 000 <210> SEQ ID NO 1449 <211> LENGTH: 915 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1449 ccgcgtgctg cacaaccgcg tacacaagct gcagcccagg ccgacgcagt atccacgaac 60 acaaattcag cgttgagtga tgctatggct tcaactcaat caattctttt ggacaccggc 120 gcatatttaa ctcgccatat cgcccaaaag tctcgtgcgg atgcagaaaa aaatagcgtg 180 tggatgtcga atactgggta tgggcgcgac tacgcctctg cgcagtaccg ccgtttcagc 240 agcaaacgca cccagactca aatcgggatc gatcgtagtc ttagtgagaa tatgcagatt 300 ggcggagttc tgacttattc cgactctcaa catacgttcg accaggcagg gggcaagaat 360 acgtttgtac aggccaatct ttacggaaag tactacttga atgatgcctg gtatgtcgct 420 ggggacattg gcgcagggag cttgcgttcc cgccttcaaa cgcaacaaaa ggcgaatttc 480 aatcgcacca gcattcagac tggccttaca cttgggaata cacttaagat taatcaattt 540 gagattgtgc ccagtgctgg gattcgttat agtcgtttat ccagcgcaga ctataagtta 600 ggcgacgact ctgtgaaagt tagctcaatg gccgtgaaga cgttgacggc tggtttggat 660 ttcgcctatc gctttaaagt tggaaatctg accgtgaagc cgctgctttc ggccgcttat 720 tttgcaaact acggcaaggg cggcgttaat gtcggtggta agagtttcgc ctataaagct 780 gacaatcagc agcaatattc ggccggcgtc gcgttgttgt atcgcaacgt gactttaaat 840 gtaaacggct ccatcacaaa gggcaagcag ttggagaagc aaaagtcagg ccaaatcaag 900 attcaaatcc gtttc 915 <210> SEQ ID NO 1450 <211> LENGTH: 696 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1450 atgttaatca atagaaacat tgtcgccctt tttgccctgc cattcatggc gagtgcgacc 60 gcttccgagt taagcatagg ggccggcgct gcgtataatg agagtcctta ccgtggctat 120 aatgaaaaca caaaggcaat cccccttatc tcgtatgaag gcgacacctt ctatgtacgt 180 cagactacat taggtttcat cttaagccag tccgagaaaa acgagttatc gctgacagct 240 tcatggatgc cattggaatt cgacccgaca gataatgatg attatgcgat gcagcagctg 300 gacaaacggg attcgacagc tatggccggc gtggcttggt atcaccacga gcggtgggga 360 actgtcaaag cttccgccgc cgctgacgtg ttagacaaca gcaatggctg ggtgggggaa 420 ttaagcgtgt tccataagat gcagataggt agattatccc ttacaccggc tttgggagtc 480 ctgtattatg atgagaactt ttccgactat tattatggga tttctgagtc tgaaagtcgt 540 cggagcggtc ttgcgtcgta ctcggcgcaa gacgcgtggg tgccttatgt atctttgaca 600 gcgaagtatc caataggcga gcacgtggta ttgatggcaa gtgctggtta ttccgagttg 660 cccgaagaaa ttactgacag tcctatgata gaccgt 696 <210> SEQ ID NO 1451 <400> SEQUENCE: 1451 000 <210> SEQ ID NO 1452 <400> SEQUENCE: 1452 000

<210> SEQ ID NO 1453 <400> SEQUENCE: 1453 000 <210> SEQ ID NO 1454 <400> SEQUENCE: 1454 000 <210> SEQ ID NO 1455 <400> SEQUENCE: 1455 000 <210> SEQ ID NO 1456 <400> SEQUENCE: 1456 000 <210> SEQ ID NO 1457 <400> SEQUENCE: 1457 000 <210> SEQ ID NO 1458 <400> SEQUENCE: 1458 000 <210> SEQ ID NO 1459 <400> SEQUENCE: 1459 000 <210> SEQ ID NO 1460 <400> SEQUENCE: 1460 000 <210> SEQ ID NO 1461 <400> SEQUENCE: 1461 000 <210> SEQ ID NO 1462 <400> SEQUENCE: 1462 000 <210> SEQ ID NO 1463 <400> SEQUENCE: 1463 000 <210> SEQ ID NO 1464 <211> LENGTH: 305 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1464 Pro Arg Ala Ala Gln Pro Arg Thr Gln Ala Ala Ala Gln Ala Asp Ala 1 5 10 15 Val Ser Thr Asn Thr Asn Ser Ala Leu Ser Asp Ala Met Ala Ser Thr 20 25 30 Gln Ser Ile Leu Leu Asp Thr Gly Ala Tyr Leu Thr Arg His Ile Ala 35 40 45 Gln Lys Ser Arg Ala Asp Ala Glu Lys Asn Ser Val Trp Met Ser Asn 50 55 60 Thr Gly Tyr Gly Arg Asp Tyr Ala Ser Ala Gln Tyr Arg Arg Phe Ser 65 70 75 80 Ser Lys Arg Thr Gln Thr Gln Ile Gly Ile Asp Arg Ser Leu Ser Glu 85 90 95 Asn Met Gln Ile Gly Gly Val Leu Thr Tyr Ser Asp Ser Gln His Thr 100 105 110 Phe Asp Gln Ala Gly Gly Lys Asn Thr Phe Val Gln Ala Asn Leu Tyr 115 120 125 Gly Lys Tyr Tyr Leu Asn Asp Ala Trp Tyr Val Ala Gly Asp Ile Gly 130 135 140 Ala Gly Ser Leu Arg Ser Arg Leu Gln Thr Gln Gln Lys Ala Asn Phe 145 150 155 160 Asn Arg Thr Ser Ile Gln Thr Gly Leu Thr Leu Gly Asn Thr Leu Lys 165 170 175 Ile Asn Gln Phe Glu Ile Val Pro Ser Ala Gly Ile Arg Tyr Ser Arg 180 185 190 Leu Ser Ser Ala Asp Tyr Lys Leu Gly Asp Asp Ser Val Lys Val Ser 195 200 205 Ser Met Ala Val Lys Thr Leu Thr Ala Gly Leu Asp Phe Ala Tyr Arg 210 215 220 Phe Lys Val Gly Asn Leu Thr Val Lys Pro Leu Leu Ser Ala Ala Tyr 225 230 235 240 Phe Ala Asn Tyr Gly Lys Gly Gly Val Asn Val Gly Gly Lys Ser Phe 245 250 255 Ala Tyr Lys Ala Asp Asn Gln Gln Gln Tyr Ser Ala Gly Val Ala Leu 260 265 270 Leu Tyr Arg Asn Val Thr Leu Asn Val Asn Gly Ser Ile Thr Lys Gly 275 280 285 Lys Gln Leu Glu Lys Gln Lys Ser Gly Gln Ile Lys Ile Gln Ile Arg 290 295 300 Phe 305 <210> SEQ ID NO 1465 <211> LENGTH: 232 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1465 Met Leu Ile Asn Arg Asn Ile Val Ala Leu Phe Ala Leu Pro Phe Met 1 5 10 15 Ala Ser Ala Thr Ala Ser Glu Leu Ser Ile Gly Ala Gly Ala Ala Tyr 20 25 30 Asn Glu Ser Pro Tyr Arg Gly Tyr Asn Glu Asn Thr Lys Ala Ile Pro 35 40 45 Leu Ile Ser Tyr Glu Gly Asp Thr Phe Tyr Val Arg Gln Thr Thr Leu 50 55 60 Gly Phe Ile Leu Ser Gln Ser Glu Lys Asn Glu Leu Ser Leu Thr Ala 65 70 75 80 Ser Trp Met Pro Leu Glu Phe Asp Pro Thr Asp Asn Asp Asp Tyr Ala 85 90 95 Met Gln Gln Leu Asp Lys Arg Asp Ser Thr Ala Met Ala Gly Val Ala 100 105 110 Trp Tyr His His Glu Arg Trp Gly Thr Val Lys Ala Ser Ala Ala Ala 115 120 125 Asp Val Leu Asp Asn Ser Asn Gly Trp Val Gly Glu Leu Ser Val Phe 130 135 140 His Lys Met Gln Ile Gly Arg Leu Ser Leu Thr Pro Ala Leu Gly Val 145 150 155 160 Leu Tyr Tyr Asp Glu Asn Phe Ser Asp Tyr Tyr Tyr Gly Ile Ser Glu 165 170 175 Ser Glu Ser Arg Arg Ser Gly Leu Ala Ser Tyr Ser Ala Gln Asp Ala 180 185 190 Trp Val Pro Tyr Val Ser Leu Thr Ala Lys Tyr Pro Ile Gly Glu His 195 200 205 Val Val Leu Met Ala Ser Ala Gly Tyr Ser Glu Leu Pro Glu Glu Ile 210 215 220 Thr Asp Ser Pro Met Ile Asp Arg 225 230 <210> SEQ ID NO 1466 <400> SEQUENCE: 1466 000 <210> SEQ ID NO 1467 <400> SEQUENCE: 1467 000 <210> SEQ ID NO 1468 <400> SEQUENCE: 1468 000 <210> SEQ ID NO 1469 <400> SEQUENCE: 1469 000 <210> SEQ ID NO 1470 <400> SEQUENCE: 1470 000 <210> SEQ ID NO 1471 <400> SEQUENCE: 1471 000 <210> SEQ ID NO 1472

<400> SEQUENCE: 1472 000 <210> SEQ ID NO 1473 <400> SEQUENCE: 1473 000 <210> SEQ ID NO 1474 <400> SEQUENCE: 1474 000 <210> SEQ ID NO 1475 <400> SEQUENCE: 1475 000 <210> SEQ ID NO 1476 <400> SEQUENCE: 1476 000 <210> SEQ ID NO 1477 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1477 Gly Gly Gly Gly Ser 1 5 <210> SEQ ID NO 1478 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1478 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 <210> SEQ ID NO 1479 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1479 Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser 1 5 10 15 <210> SEQ ID NO 1480 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1480 Glu Ala Ala Ala Lys 1 5 <210> SEQ ID NO 1481 <211> LENGTH: 10 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1481 Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys 1 5 10 <210> SEQ ID NO 1482 <211> LENGTH: 15 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1482 Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys 1 5 10 15 <210> SEQ ID NO 1483 <211> LENGTH: 173 <212> TYPE: PRT <213> ORGANISM: Escherichia coli <400> SEQUENCE: 1483 Met Gln Leu Asn Lys Val Leu Lys Gly Leu Met Ile Ala Leu Pro Val 1 5 10 15 Met Ala Ile Ala Ala Cys Ser Ser Asn Lys Asn Ala Ser Asn Asp Gly 20 25 30 Ser Glu Gly Met Leu Gly Ala Gly Thr Gly Met Asp Ala Asn Gly Gly 35 40 45 Asn Gly Asn Met Ser Ser Glu Glu Gln Ala Arg Leu Gln Met Gln Gln 50 55 60 Leu Gln Gln Asn Asn Ile Val Tyr Phe Asp Leu Asp Lys Tyr Asp Ile 65 70 75 80 Arg Ser Asp Phe Ala Gln Met Leu Asp Ala His Ala Asn Phe Leu Arg 85 90 95 Ser Asn Pro Ser Tyr Lys Val Thr Val Glu Gly His Ala Asp Glu Arg 100 105 110 Gly Thr Pro Glu Tyr Asn Ile Ser Leu Gly Glu Arg Arg Ala Asn Ala 115 120 125 Val Lys Met Tyr Leu Gln Gly Lys Gly Val Ser Ala Asp Gln Ile Ser 130 135 140 Ile Val Ser Tyr Gly Lys Glu Lys Pro Ala Val Leu Gly His Asp Glu 145 150 155 160 Ala Ala Tyr Ala Lys Asn Arg Arg Ala Val Leu Val Tyr 165 170 <210> SEQ ID NO 1484 <211> LENGTH: 4307 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1484 tagcggagtg tatactggct tactatgttg gcactgatga gggtgtcagt gaagtgcttc 60 atgtggcagg agaaaaaagg ctgcaccggt gcgtcagcag aatatgtgat acaggatata 120 ttccgcttcc tcgctcactg actcgctacg ctcggtcgtt cgactgcggc gagcggaaat 180 ggcttacgaa cggggcggag atttcctgga agatgccagg aagatactta acagggaagt 240 gagagggccg cggcaaagcc gtttttccat aggctccgcc cccctgacaa gcatcacgaa 300 atctgacgct caaatcagtg gtggcgaaac ccgacaggac tataaagata ccaggcgttt 360 cccctggcgg ctccctcgtg cgctctcctg ttcctgcctt tcggtttacc ggtgtcattc 420 cgctgttatg gccgcgtttg tctcattcca cgcctgacac tcagttccgg gtaggcagtt 480 cgctccaagc tggactgtat gcacgaaccc cccgttcagt ccgaccgctg cgccttatcc 540 ggtaactatc gtcttgagtc caacccggaa agacatgcaa aagcaccact ggcagcagcc 600 actggtaatt gatttagagg agttagtctt gaagtcatgc gccggttaag gctaaactga 660 aaggacaagt tttggtgact gcgctcctcc aagccagtta cctcggttca aagagttggt 720 agctcagaga accttcgaaa aaccgccctg caaggcggtt ttttcgtttt cagagcaaga 780 gattacgcgc agaccaaaac gatctcaaga agatcatctt attaaggggt ctgacgctca 840 gtggaacggt gcaccctgca gggctagctg ataaagcgtt cgcgctgcat tcggcagttt 900 aagacccact ttcacattta agttgttttt ctaatccgca tatgatcaat tcaaggccga 960 ataagaaggc tggctctgca ccttggtgat caaataattc gatagcttgt cgtaataatg 1020 gcggcatact atcagtagta ggtgtttccc tttcttcttt agcgacttga tgctcttgat 1080 cttccaatac gcaacctaaa gtaaaatgcc ccacagcgct gagtgcatat aatgcattct 1140 ctagtgaaaa accttgttgg cataaaaagg ctaattgatt ttcgagagtt tcatactgtt 1200 tttctgtagg ccgtgtacct aaatgtactt ttgctccatc gcgatgactt agtaaagcac 1260 atctaaaact tttagcgtta ttacgtaaaa aatcttgcca gctttcccct tctaaagggc 1320 aaaagtgagt atggtgccta tctaacatct caatggctaa ggcgtcgagc aaagcccgct 1380 tattttttac atgccaatac aatgtaggct gctctacacc tagcttctgg gcgagtttac 1440 gggttgttaa accttcgatt ccgacctcat taagcagctc taatgcgctg ttaatcactt 1500 tacttttatc taatctagac atcattaatt cctaattttt gttgacactc tatcattgat 1560 agagttattt taccactccc tatcagtgat agagaaaagt gaaaggaggt aaattatgaa 1620 atatcttctt ccaacggctg ctgctggttt attgcttctt gccgcccagc ctgcgatggc 1680 tactagtgac tataaggatg acgacgacaa gagatctacg gcattgacgg aaggtgcaaa 1740 actgtttgag aaagagatcc cgtatatcac cgaactggaa ggcgacgtcg aaggtatgaa 1800 atttatcatt aaaggcgagg gtaccggtga cgcgaccacg ggtaccatta aagcgaaata 1860 catctgcact acgggcgacc tgccggtccc gtgggcaacc ctggtgagca ccctgagcta 1920 cggtgttcag tgtttcgcca agtacccgag ccacatcaag gatttcttta agagcgccat 1980 gccggaaggt tatacccaag agcgtaccat cagcttcgaa ggcgacggcg tgtacaagac 2040 gcgtgctatg gttacctacg aacgcggttc tatctacaat cgtgtcacgc tgactggtga 2100 gaactttaag aaagacggtc acattctgcg taagaacgtt gcattccaat gcccgccaag 2160 cattctgtat attctgcctg acaccgttaa caatggcatc cgcgttgagt tcaaccaggc 2220 gtacgatatt gaaggtgtga ccgaaaaact ggttaccaaa tgcagccaaa tgaatcgtcc 2280

gttggcgggc tccgcggcag tgcatatccc gcgttatcat cacattacct accacaccaa 2340 actgagcaaa gaccgcgacg agcgccgtga tcacatgtgt ctggtagagg tcgtgaaagc 2400 ggttgatctg gacacgtatc agggatccgg ccaccaccat catcaccact gcagtagcaa 2460 taaaaatgct tcgaatgacg gatcggaagg aatgttaggt gctggtactg gcatggacgc 2520 caacggtggc aacggaaata tgtctagcga agaacaagct cgtttacaaa tgcagcaatt 2580 acagcaaaac aacatagtct acttcgactt agacaagtac gacatccgta gcgattttgc 2640 acaaatgttg gatgcccatg ccaacttcct tcgttctaat ccaagctaca aagtcactgt 2700 tgagggccac gcggatgaga gaggcactcc tgaatataac atatccctgg gggagcgcag 2760 agcaaacgcc gtaaaaatgt acctgcaagg caagggcgtc tcggccgatc aaatctcgat 2820 cgtgagctat ggcaaagaga aaccggctgt attgggacat gacgaagctg cttacagcaa 2880 gaatcggcgg gccgtcttgg tctactaata agcatgctaa tcagccgtgg aattcgcaac 2940 gtaaaaaaac ccgccccggc gggttttttt ataccggtct caggaggaac gattggtaaa 3000 cccggtgaac gcatgagaaa gcccccggaa gatcaccttc cgggggcttt tttattgcgc 3060 ggaccaaaac gaaaaaagac gctcgaaagc gtctcttttc tggaatttgg taccgaggcg 3120 taatgctctg ccagtgttac aaccaattaa ccaattctga ttagaaaaac tcatcgagca 3180 tcaaatgaaa ctgcaattta ttcatatcag gattatcaat accatatttt tgaaaaagcc 3240 gtttctgtaa tgaaggagaa aactcaccga ggcagttcca taggatggca agatcctggt 3300 atcggtctgc gattccgact cgtccaacat caatacaacc tattaatttc ccctcgtcaa 3360 aaataaggtt atcaagtgag aaatcaccat gagtgacgac tgaatccggt gagaatggca 3420 aaagcttatg catttctttc cagacttgtt caacaggcca gccattacgc tcgtcatcaa 3480 aatcactcgc atcaaccaaa ccgttattca ttcgtgattg cgcctgagcg agacgaaata 3540 cgcgatcgct gttaaaagga caattacaaa caggaatcga atgcaaccgg cgcaggaaca 3600 ctgccagcgc atcaacaata ttttcacctg aatcaggata ttcttctaat acctggaatg 3660 ctgttttccc ggggatcgca gtggtgagta accatgcatc atcaggagta cggataaaat 3720 gcttgatggt cggaagaggc ataaattccg tcagccagtt tagtctgacc atctcatctg 3780 taacatcatt ggcaacgcta cctttgccat gtttcagaaa caactctggc gcatcgggct 3840 tcccatacaa tcgatagatt gtcgcacctg attgcccgac attatcgcga gcccatttat 3900 acccatataa atcagcatcc atgttggaat ttaatcgcgg cctcgagcaa gacgtttccc 3960 gttgaatatg gctcataaca ccccttgtat tactgtttat gtaagcagac agttttattg 4020 ttcatgatga tatattttta tcttgtgcaa tgtaacatca gagattttga gacacaacgt 4080 ggctttgttg aataaatcga acttttgctg agttgaagga tcagatcacg catcttcccg 4140 acaacgcaga ccgttccgtg gcaaagcaaa agttcaaaat caccaactgg tccacctaca 4200 acaaagctct catcaaccgt ggctccctca ctttctggct ggatgatggg gcgattcagg 4260 cctggtatga gtcagcaaca ccttcttcac gaggcagacc tcagcgc 4307 <210> SEQ ID NO 1485 <211> LENGTH: 3811 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1485 tagcggagtg tatactggct tactatgttg gcactgatga gggtgtcagt gaagtgcttc 60 atgtggcagg agaaaaaagg ctgcaccggt gcgtcagcag aatatgtgat acaggatata 120 ttccgcttcc tcgctcactg actcgctacg ctcggtcgtt cgactgcggc gagcggaaat 180 ggcttacgaa cggggcggag atttcctgga agatgccagg aagatactta acagggaagt 240 gagagggccg cggcaaagcc gtttttccat aggctccgcc cccctgacaa gcatcacgaa 300 atctgacgct caaatcagtg gtggcgaaac ccgacaggac tataaagata ccaggcgttt 360 cccctggcgg ctccctcgtg cgctctcctg ttcctgcctt tcggtttacc ggtgtcattc 420 cgctgttatg gccgcgtttg tctcattcca cgcctgacac tcagttccgg gtaggcagtt 480 cgctccaagc tggactgtat gcacgaaccc cccgttcagt ccgaccgctg cgccttatcc 540 ggtaactatc gtcttgagtc caacccggaa agacatgcaa aagcaccact ggcagcagcc 600 actggtaatt gatttagagg agttagtctt gaagtcatgc gccggttaag gctaaactga 660 aaggacaagt tttggtgact gcgctcctcc aagccagtta cctcggttca aagagttggt 720 agctcagaga accttcgaaa aaccgccctg caaggcggtt ttttcgtttt cagagcaaga 780 gattacgcgc agaccaaaac gatctcaaga agatcatctt attaaggggt ctgacgctca 840 gtggaacggt gcaccctgca gggctagctg ataaagcgtt cgcgctgcat tcggcagttt 900 aagacccact ttcacattta agttgttttt ctaatccgca tatgatcaat tcaaggccga 960 ataagaaggc tggctctgca ccttggtgat caaataattc gatagcttgt cgtaataatg 1020 gcggcatact atcagtagta ggtgtttccc tttcttcttt agcgacttga tgctcttgat 1080 cttccaatac gcaacctaaa gtaaaatgcc ccacagcgct gagtgcatat aatgcattct 1140 ctagtgaaaa accttgttgg cataaaaagg ctaattgatt ttcgagagtt tcatactgtt 1200 tttctgtagg ccgtgtacct aaatgtactt ttgctccatc gcgatgactt agtaaagcac 1260 atctaaaact tttagcgtta ttacgtaaaa aatcttgcca gctttcccct tctaaagggc 1320 aaaagtgagt atggtgccta tctaacatct caatggctaa ggcgtcgagc aaagcccgct 1380 tattttttac atgccaatac aatgtaggct gctctacacc tagcttctgg gcgagtttac 1440 gggttgttaa accttcgatt ccgacctcat taagcagctc taatgcgctg ttaatcactt 1500 tacttttatc taatctagac atcattaatt cctaattttt gttgacactc tatcattgat 1560 agagttattt taccactccc tatcagtgat agagaaaagt gaaaggaggt aaattatgac 1620 tagtgctttt gaccccaatc tggttgggcc tacgttacct ccaattccgc ctttcactct 1680 gcctacggac tataaggatg acgacgacaa gagatctacg gcattgacgg aaggtgcaaa 1740 actgtttgag aaagagatcc cgtatatcac cgaactggaa ggcgacgtcg aaggtatgaa 1800 atttatcatt aaaggcgagg gtaccggtga cgcgaccacg ggtaccatta aagcgaaata 1860 catctgcact acgggcgacc tgccggtccc gtgggcaacc ctggtgagca ccctgagcta 1920 cggtgttcag tgtttcgcca agtacccgag ccacatcaag gatttcttta agagcgccat 1980 gccggaaggt tatacccaag agcgtaccat cagcttcgaa ggcgacggcg tgtacaagac 2040 gcgtgctatg gttacctacg aacgcggttc tatctacaat cgtgtcacgc tgactggtga 2100 gaactttaag aaagacggtc acattctgcg taagaacgtt gcattccaat gcccgccaag 2160 cattctgtat attctgcctg acaccgttaa caatggcatc cgcgttgagt tcaaccaggc 2220 gtacgatatt gaaggtgtga ccgaaaaact ggttaccaaa tgcagccaaa tgaatcgtcc 2280 gttggcgggc tccgcggcag tgcatatccc gcgttatcat cacattacct accacaccaa 2340 actgagcaaa gaccgcgacg agcgccgtga tcacatgtgt ctggtagagg tcgtgaaagc 2400 ggttgatctg gacacgtatc agggatccgg ccaccaccat catcaccact aataagcatg 2460 ctaatcagcc gtggaattcg gtctcaggag gaacgattgg taaacccggt gaacgcatga 2520 gaaagccccc ggaagatcac cttccggggg cttttttatt gcgcggacca aaacgaaaaa 2580 agacgctcga aagcgtctct tttctggaat ttggtaccga ggcgtaatgc tctgccagtg 2640 ttacaaccaa ttaaccaatt ctgattagaa aaactcatcg agcatcaaat gaaactgcaa 2700 tttattcata tcaggattat caataccata tttttgaaaa agccgtttct gtaatgaagg 2760 agaaaactca ccgaggcagt tccataggat ggcaagatcc tggtatcggt ctgcgattcc 2820 gactcgtcca acatcaatac aacctattaa tttcccctcg tcaaaaataa ggttatcaag 2880 tgagaaatca ccatgagtga cgactgaatc cggtgagaat ggcaaaagct tatgcatttc 2940 tttccagact tgttcaacag gccagccatt acgctcgtca tcaaaatcac tcgcatcaac 3000 caaaccgtta ttcattcgtg attgcgcctg agcgagacga aatacgcgat cgctgttaaa 3060 aggacaatta caaacaggaa tcgaatgcaa ccggcgcagg aacactgcca gcgcatcaac 3120 aatattttca cctgaatcag gatattcttc taatacctgg aatgctgttt tcccggggat 3180 cgcagtggtg agtaaccatg catcatcagg agtacggata aaatgcttga tggtcggaag 3240 aggcataaat tccgtcagcc agtttagtct gaccatctca tctgtaacat cattggcaac 3300 gctacctttg ccatgtttca gaaacaactc tggcgcatcg ggcttcccat acaatcgata 3360 gattgtcgca cctgattgcc cgacattatc gcgagcccat ttatacccat ataaatcagc 3420 atccatgttg gaatttaatc gcggcctcga gcaagacgtt tcccgttgaa tatggctcat 3480 aacacccctt gtattactgt ttatgtaagc agacagtttt attgttcatg atgatatatt 3540 tttatcttgt gcaatgtaac atcagagatt ttgagacaca acgtggcttt gttgaataaa 3600 tcgaactttt gctgagttga aggatcagat cacgcatctt cccgacaacg cagaccgttc 3660 cgtggcaaag caaaagttca aaatcaccaa ctggtccacc tacaacaaag ctctcatcaa 3720 ccgtggctcc ctcactttct ggctggatga tggggcgatt caggcctggt atgagtcagc 3780 aacaccttct tcacgaggca gacctcagcg c 3811 <210> SEQ ID NO 1486 <211> LENGTH: 4195 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1486 tggcataaaa aggctaattg attttcgaga gtttcatact gtttttctgt aggccgtgta 60 cctaaatgta cttttgctcc atcgcgatga cttagtaaag cacatctaaa acttttagcg 120 ttattacgta aaaaatcttg ccagctttcc ccttctaaag ggcaaaagtg agtatggtgc 180 ctatctaaca tctcaatggc taaggcgtcg agcaaagccc gcttattttt tacatgccaa 240 tacaatgtag gctgctctac acctagcttc tgggcgagtt tacgggttgt taaaccttcg 300 attccgacct cattaagcag ctctaatgcg ctgttaatca ctttactttt atctaatcta 360 gacatcatta attcctaatt tttgttgaca ctctatcatt gatagagtta ttttaccact 420 ccctatcagt gatagagaaa agtgaaagga ggtaaattat gactagtaaa gcaacaaaac 480 ttgtgttagg cgcggttata cttggctcca ccctgcttgc aggttgctcg tctaacgcga 540 agatcgacca gggtatcaat ccttacgtcg ggtttgaaat gggatacgat tggttgggac 600 gtatgcctta taagggaagt gttgaaaacg gcgcttataa ggcgcaggga gtacagttaa 660 cggccaagct tgggtacccc ataacagacg atttagatat ttatacccgt ttaggaggaa 720 tggtttggag agccgacacg aagtctaatg tatatggtaa gaaccacgac acgggagtat 780 cccccgtctt tgcaggggga gtggaatatg ctatcacacc agagatcgct acccgtttgg 840 aatatcaatg gacgaataat ataggcgacg cccatacgat aggaacgcgg cccgacaacg 900 gcatccctgg ggtcgactat aaggatgacg acgacaagca attgacggca ttgacggaag 960

gtgcaaaact gtttgagaaa gagatcccgt atatcaccga actggaaggc gacgtcgaag 1020 gtatgaaatt tatcattaaa ggcgagggta ccggtgacgc gaccacgggt accattaaag 1080 cgaaatacat ctgcactacg ggcgacctgc cggtcccgtg ggcaaccctg gtgagcaccc 1140 tgagctacgg tgttcagtgt ttcgccaagt acccgagcca catcaaggat ttctttaaga 1200 gcgccatgcc ggaaggttat acccaagagc gtaccatcag cttcgaaggc gacggcgtgt 1260 acaagacgcg tgctatggtt acctacgaac gcggttctat ctacaatcgt gtcacgctga 1320 ctggtgagaa ctttaagaaa gacggtcaca ttctgcgtaa gaacgttgca ttccaatgcc 1380 cgccaagcat tctgtatatt ctgcctgaca ccgttaacaa tggcatccgc gttgagttca 1440 accaggcgta cgatattgaa ggtgtgaccg aaaaactggt taccaaatgc agccaaatga 1500 atcgtccgtt ggcgggctcc gcggcagtgc atatcccgcg ttatcatcac attacctacc 1560 acaccaaact gagcaaagac cgcgacgagc gccgtgatca catgtgtctg gtagaggtcg 1620 tgaaagcggt tgatctggac acgtatcagg gatccggcca ccaccatcat caccactaat 1680 aagcatgcta atcagccgtg gaattcggtc tcaggaggaa cgattggtaa acccggtgaa 1740 cgcatgagaa agcccccgga agatcacctt ccgggggctt ttttattgcg cggaccaaaa 1800 cgaaaaaaga cgctcgaaag cgtctctttt ctggaatttg gtaccgaggc gtaatgctct 1860 gccagtgtta caaccaatta accaattctg attagaaaaa ctcatcgagc atcaaatgaa 1920 actgcaattt attcatatca ggattatcaa taccatattt ttgaaaaagc cgtttctgta 1980 atgaaggaga aaactcaccg aggcagttcc ataggatggc aagatcctgg tatcggtctg 2040 cgattccgac tcgtccaaca tcaatacaac ctattaattt cccctcgtca aaaataaggt 2100 tatcaagtga gaaatcacca tgagtgacga ctgaatccgg tgagaatggc aaaagcttat 2160 gcatttcttt ccagacttgt tcaacaggcc agccattacg ctcgtcatca aaatcactcg 2220 catcaaccaa accgttattc attcgtgatt gcgcctgagc gagacgaaat acgcgatcgc 2280 tgttaaaagg acaattacaa acaggaatcg aatgcaaccg gcgcaggaac actgccagcg 2340 catcaacaat attttcacct gaatcaggat attcttctaa tacctggaat gctgttttcc 2400 cggggatcgc agtggtgagt aaccatgcat catcaggagt acggataaaa tgcttgatgg 2460 tcggaagagg cataaattcc gtcagccagt ttagtctgac catctcatct gtaacatcat 2520 tggcaacgct acctttgcca tgtttcagaa acaactctgg cgcatcgggc ttcccataca 2580 atcgatagat tgtcgcacct gattgcccga cattatcgcg agcccattta tacccatata 2640 aatcagcatc catgttggaa tttaatcgcg gcctcgagca agacgtttcc cgttgaatat 2700 ggctcataac accccttgta ttactgttta tgtaagcaga cagttttatt gttcatgatg 2760 atatattttt atcttgtgca atgtaacatc agagattttg agacacaacg tggctttgtt 2820 gaataaatcg aacttttgct gagttgaagg atcagatcac gcatcttccc gacaacgcag 2880 accgttccgt ggcaaagcaa aagttcaaaa tcaccaactg gtccacctac aacaaagctc 2940 tcatcaaccg tggctccctc actttctggc tggatgatgg ggcgattcag gcctggtatg 3000 agtcagcaac accttcttca cgaggcagac ctcagcgcta gcggagtgta tactggctta 3060 ctatgttggc actgatgagg gtgtcagtga agtgcttcat gtggcaggag aaaaaaggct 3120 gcaccggtgc gtcagcagaa tatgtgatac aggatatatt ccgcttcctc gctcactgac 3180 tcgctacgct cggtcgttcg actgcggcga gcggaaatgg cttacgaacg gggcggagat 3240 ttcctggaag atgccaggaa gatacttaac agggaagtga gagggccgcg gcaaagccgt 3300 ttttccatag gctccgcccc cctgacaagc atcacgaaat ctgacgctca aatcagtggt 3360 ggcgaaaccc gacaggacta taaagatacc aggcgtttcc cctggcggct ccctcgtgcg 3420 ctctcctgtt cctgcctttc ggtttaccgg tgtcattccg ctgttatggc cgcgtttgtc 3480 tcattccacg cctgacactc agttccgggt aggcagttcg ctccaagctg gactgtatgc 3540 acgaaccccc cgttcagtcc gaccgctgcg ccttatccgg taactatcgt cttgagtcca 3600 acccggaaag acatgcaaaa gcaccactgg cagcagccac tggtaattga tttagaggag 3660 ttagtcttga agtcatgcgc cggttaaggc taaactgaaa ggacaagttt tggtgactgc 3720 gctcctccaa gccagttacc tcggttcaaa gagttggtag ctcagagaac cttcgaaaaa 3780 ccgccctgca aggcggtttt ttcgttttca gagcaagaga ttacgcgcag accaaaacga 3840 tctcaagaag atcatcttat taaggggtct gacgctcagt ggaacggtgc accctgcagg 3900 gctagctgat aaagcgttcg cgctgcattc ggcagtttaa gacccacttt cacatttaag 3960 ttgtttttct aatccgcata tgatcaattc aaggccgaat aagaaggctg gctctgcacc 4020 ttggtgatca aataattcga tagcttgtcg taataatggc ggcatactat cagtagtagg 4080 tgtttccctt tcttctttag cgacttgatg ctcttgatct tccaatacgc aacctaaagt 4140 aaaatgcccc acagcgctga gtgcatataa tgcattctct agtgaaaaac cttgt 4195 <210> SEQ ID NO 1487 <211> LENGTH: 4744 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1487 aacgaaaaaa gacgctcgaa agcgtctctt ttctggaatt tggtaccgag gcgtaatgct 60 ctgccagtgt tacaaccaat taaccaattc tgattagaaa aactcatcga gcatcaaatg 120 aaactgcaat ttattcatat caggattatc aataccatat ttttgaaaaa gccgtttctg 180 taatgaagga gaaaactcac cgaggcagtt ccataggatg gcaagatcct ggtatcggtc 240 tgcgattccg actcgtccaa catcaataca acctattaat ttcccctcgt caaaaataag 300 gttatcaagt gagaaatcac catgagtgac gactgaatcc ggtgagaatg gcaaaagctt 360 atgcatttct ttccagactt gttcaacagg ccagccatta cgctcgtcat caaaatcact 420 cgcatcaacc aaaccgttat tcattcgtga ttgcgcctga gcgagacgaa atacgcgatc 480 gctgttaaaa ggacaattac aaacaggaat cgaatgcaac cggcgcagga acactgccag 540 cgcatcaaca atattttcac ctgaatcagg atattcttct aatacctgga atgctgtttt 600 cccggggatc gcagtggtga gtaaccatgc atcatcagga gtacggataa aatgcttgat 660 ggtcggaaga ggcataaatt ccgtcagcca gtttagtctg accatctcat ctgtaacatc 720 attggcaacg ctacctttgc catgtttcag aaacaactct ggcgcatcgg gcttcccata 780 caatcgatag attgtcgcac ctgattgccc gacattatcg cgagcccatt tatacccata 840 taaatcagca tccatgttgg aatttaatcg cggcctcgag caagacgttt cccgttgaat 900 atggctcata acaccccttg tattactgtt tatgtaagca gacagtttta ttgttcatga 960 tgatatattt ttatcttgtg caatgtaaca tcagagattt tgagacacaa cgtggctttg 1020 ttgaataaat cgaacttttg ctgagttgaa ggatcagatc acgcatcttc ccgacaacgc 1080 agaccgttcc gtggcaaagc aaaagttcaa aatcaccaac tggtccacct acaacaaagc 1140 tctcatcaac cgtggctccc tcactttctg gctggatgat ggggcgattc aggcctggta 1200 tgagtcagca acaccttctt cacgaggcag acctcagcgc tagcggagtg tatactggct 1260 tactatgttg gcactgatga gggtgtcagt gaagtgcttc atgtggcagg agaaaaaagg 1320 ctgcaccggt gcgtcagcag aatatgtgat acaggatata ttccgcttcc tcgctcactg 1380 actcgctacg ctcggtcgtt cgactgcggc gagcggaaat ggcttacgaa cggggcggag 1440 atttcctgga agatgccagg aagatactta acagggaagt gagagggccg cggcaaagcc 1500 gtttttccat aggctccgcc cccctgacaa gcatcacgaa atctgacgct caaatcagtg 1560 gtggcgaaac ccgacaggac tataaagata ccaggcgttt cccctggcgg ctccctcgtg 1620 cgctctcctg ttcctgcctt tcggtttacc ggtgtcattc cgctgttatg gccgcgtttg 1680 tctcattcca cgcctgacac tcagttccgg gtaggcagtt cgctccaagc tggactgtat 1740 gcacgaaccc cccgttcagt ccgaccgctg cgccttatcc ggtaactatc gtcttgagtc 1800 caacccggaa agacatgcaa aagcaccact ggcagcagcc actggtaatt gatttagagg 1860 agttagtctt gaagtcatgc gccggttaag gctaaactga aaggacaagt tttggtgact 1920 gcgctcctcc aagccagtta cctcggttca aagagttggt agctcagaga accttcgaaa 1980 aaccgccctg caaggcggtt ttttcgtttt cagagcaaga gattacgcgc agaccaaaac 2040 gatctcaaga agatcatctt attaaggggt ctgacgctca gtggaacggt gcaccctgca 2100 gggctagctg ataaagcgtt cgcgctgcat tcggcagttt aagacccact ttcacattta 2160 agttgttttt ctaatccgca tatgatcaat tcaaggccga ataagaaggc tggctctgca 2220 ccttggtgat caaataattc gatagcttgt cgtaataatg gcggcatact atcagtagta 2280 ggtgtttccc tttcttcttt agcgacttga tgctcttgat cttccaatac gcaacctaaa 2340 gtaaaatgcc ccacagcgct gagtgcatat aatgcattct ctagtgaaaa accttgttgg 2400 cataaaaagg ctaattgatt ttcgagagtt tcatactgtt tttctgtagg ccgtgtacct 2460 aaatgtactt ttgctccatc gcgatgactt agtaaagcac atctaaaact tttagcgtta 2520 ttacgtaaaa aatcttgcca gctttcccct tctaaagggc aaaagtgagt atggtgccta 2580 tctaacatct caatggctaa ggcgtcgagc aaagcccgct tattttttac atgccaatac 2640 aatgtaggct gctctacacc tagcttctgg gcgagtttac gggttgttaa accttcgatt 2700 ccgacctcat taagcagctc taatgcgctg ttaatcactt tacttttatc taatctagac 2760 atcattaatt cctaattttt gttgacactc tatcattgat agagttattt taccactccc 2820 tatcagtgat agagaaaagt gaaaggaggt aaattatgac tagtaaggca aaacgcttca 2880 agattaacgc tatcagttta tccatctttt tagcgtatgc gttgactccg tactcagagg 2940 cagtcgacta taaggatgac gacgacaagc aattgacggc attgacggaa ggtgcaaaac 3000 tgtttgagaa agagatcccg tatatcaccg aactggaagg cgacgtcgaa ggtatgaaat 3060 ttatcattaa aggcgagggt accggtgacg cgaccacggg taccattaaa gcgaaataca 3120 tctgcactac gggcgacctg ccggtcccgt gggcaaccct ggtgagcacc ctgagctacg 3180 gtgttcagtg tttcgccaag tacccgagcc acatcaagga tttctttaag agcgccatgc 3240 cggaaggtta tacccaagag cgtaccatca gcttcgaagg cgacggcgtg tacaagacgc 3300 gtgctatggt tacctacgaa cgcggttcta tctacaatcg tgtcacgctg actggtgaga 3360 actttaagaa agacggtcac attctgcgta agaacgttgc attccaatgc ccgccaagca 3420 ttctgtatat tctgcctgac accgttaaca atggcatccg cgttgagttc aaccaggcgt 3480 acgatattga aggtgtgacc gaaaaactgg ttaccaaatg cagccaaatg aatcgtccgt 3540 tggcgggctc cgcggcagtg catatcccgc gttatcatca cattacctac cacaccaaac 3600 tgagcaaaga ccgcgacgag cgccgtgatc acatgtgtct ggtagaggtc gtgaaagcgg 3660 ttgatctgga cacgtatcag ggatccggcc accaccatca tcaccacccg cgtgctgcac 3720 aaccgcgtac acaagctgca gcccaggccg acgcagtatc cacgaacaca aattcagcgt 3780 tgagtgatgc tatggcttca actcaatcaa ttcttttgga caccggcgca tatttaactc 3840 gccatatcgc ccaaaagtct cgtgcggatg cagaaaaaaa tagcgtgtgg atgtcgaata 3900

ctgggtatgg gcgcgactac gcctctgcgc agtaccgccg tttcagcagc aaacgcaccc 3960 agactcaaat cgggatcgat cgtagtctta gtgagaatat gcagattggc ggagttctga 4020 cttattccga ctctcaacat acgttcgacc aggcaggggg caagaatacg tttgtacagg 4080 ccaatcttta cggaaagtac tacttgaatg atgcctggta tgtcgctggg gacattggcg 4140 cagggagctt gcgttcccgc cttcaaacgc aacaaaaggc gaatttcaat cgcaccagca 4200 ttcagactgg ccttacactt gggaatacac ttaagattaa tcaatttgag attgtgccca 4260 gtgctgggat tcgttatagt cgtttatcca gcgcagacta taagttaggc gacgactctg 4320 tgaaagttag ctcaatggcc gtgaagacgt tgacggctgg tttggatttc gcctatcgct 4380 ttaaagttgg aaatctgacc gtgaagccgc tgctttcggc cgcttatttt gcaaactacg 4440 gcaagggcgg cgttaatgtc ggtggtaaga gtttcgccta taaagctgac aatcagcagc 4500 aatattcggc cggcgtcgcg ttgttgtatc gcaacgtgac tttaaatgta aacggctcca 4560 tcacaaaggg caagcagttg gagaagcaaa agtcaggcca aatcaagatt caaatccgtt 4620 tctaataagc atgctaatca gccgtggaat tcggtctcag gaggaacgat tggtaaaccc 4680 ggtgaacgca tgagaaagcc cccggaagat caccttccgg gggctttttt attgcgcgga 4740 ccaa 4744 <210> SEQ ID NO 1488 <211> LENGTH: 56 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1488 gttgacactc tatcattgat agagttattt taccactccc tatcagtgat agagaa 56 <210> SEQ ID NO 1489 <211> LENGTH: 456 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1489 tgcagtagca ataaaaatgc ttcgaatgac ggatcggaag gaatgttagg tgctggtact 60 ggcatggacg ccaacggtgg caacggaaat atgtctagcg aagaacaagc tcgtttacaa 120 atgcagcaat tacagcaaaa caacatagtc tacttcgact tagacaagta cgacatccgt 180 agcgattttg cacaaatgtt ggatgcccat gccaacttcc ttcgttctaa tccaagctac 240 aaagtcactg ttgagggcca cgcggatgag agaggcactc ctgaatataa catatccctg 300 ggggagcgca gagcaaacgc cgtaaaaatg tacctgcaag gcaagggcgt ctcggccgat 360 caaatctcga tcgtgagcta tggcaaagag aaaccggctg tattgggaca tgacgaagct 420 gcttacagca agaatcggcg ggccgtcttg gtctac 456 <210> SEQ ID NO 1490 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1490 gcttttgacc ccaatctggt tgggcctacg ttacctccaa ttccgccttt cactctgcct 60 acg 63 <210> SEQ ID NO 1491 <211> LENGTH: 442 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1491 atgactagtt aaagcaacaa aacttgtgtt aggcgcggtt atacttggct ccaccctgct 60 tgcaggttgc tcgtctaacg cgaagatcga ccagggtatc aatccttacg tcgggtttga 120 aatgggatac gattggttgg gacgtatgcc ttataaggga agtgttgaaa acggcgctta 180 taaggcgcag ggagtacagt taacggccaa gcttgggtac cccataacag acgatttaga 240 tatttatacc cgtttaggag gaatggtttg gagagccgac acgaagtcta atgtatatgg 300 taagaaccac gacacgggag tatcccccgt ctttgcaggg ggagtggaat atgctatcac 360 accagagatc gctacccgtt tggaatatca atggacgaat aatataggcg acgcccatac 420 gataggaacg cggcccgaca ac 442 <210> SEQ ID NO 1492 <211> LENGTH: 603 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1492 atgacaatga ctcgtttgaa aatttccaaa accctgctgg ccgtaatgct tacgtccgca 60 gtcgccactg gttccgcata cgcagagaat aatgcgcaga caactaacga gtcagcaggg 120 caaaaagtag actccagtat gaataaggtg ggcaatttta tggacgactc agctatcacc 180 gctaaggtga aagcggcgct ggtggaccac gacaacatca agtccacgga catctcagtt 240 aaaacggacc aaaaggtagt aaccttaagc gggttcgtag aaagccaggc gcaagcagag 300 gaagcggtaa aagtcgctaa aggcgtagaa ggggtcactt cggtgtcaga caagttgcat 360 gtgcgtgacg caaaggaagg atcagtaaag ggttatgccg gagatacggc aacgacctct 420 gagatcaaag cgaaattact ggcagacgac attgttccct cgcgtcatgt taaagtcgaa 480 acgactgatg gcgtagtcca gctttcgggt acagttgact cccaagcaca aagtgatcgc 540 gcggaatcta ttgcaaaggc ggtggacgga gtgaaatccg tcaaaaacga tcttaaaacg 600 aaa 603 <210> SEQ ID NO 1493 <211> LENGTH: 1820 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1493 atggttttcc aacccatcag cgaatttttg ctgattcgta acgctgggat gtccatgtat 60 tttaacaaga tcatttcttt taacatcatt tcacgtatcg ttatttgcat ttttcttatc 120 tgtggtatgt tcatggccgg tgcatctgaa aagtatgatg caaacgcacc ccaacaggtg 180 cagccatact cggtttcatc atcagcgttc gagaatctgc accccaataa cgagatggag 240 tcgagtatca acccttttag tgcttcggac accgagcgta atgcagctat catcgatcgt 300 gctaacaagg aacaagaaac ggaagcagtc aacaaaatga tctccactgg cgctcgttta 360 gctgccagcg gtcgcgcgtc cgatgtggcg cacagtatgg taggggatgc ggtcaaccag 420 gagattaaac aatggctgaa tcgcttcggc actgctcaag tgaatttaaa ttttgacaag 480 aacttctcgt taaaggagtc ttcgcttgac tggttggccc catggtacga ttcggcgtca 540 ttccttttct tttctcagtt gggcatccgt aacaaggaca gtcgtaatac acttaacctt 600 ggtgttggca ttcgcacatt agaaaatggt tggttgtatg gcctgaacac cttttacgac 660 aatgacttaa cgggacacaa tcaccgtatc gggctgggcg ccgaggcgtg gactgactac 720 ttgcagttag ccgcgaatgg gtacttccgt cttaatggtt ggcactcttc ccgtgacttc 780 agcgactaca aagaacgccc tgctaccggg ggagatttgc gtgcgaatgc gtacctgccc 840 gctcttccgc aacttggcgg gaagttaatg tatgagcagt atactgggga acgcgtggct 900 ctgttcggaa aggacaacct gcagcgcaac ccatacgctg tcactgcggg tatcaactat 960 acgccagttc cgttgctgac ggtcggcgtg gatcaacgta tggggaagtc gagtaaacat 1020 gaaacgcaat ggaatttaca aatgaactat cgcttagggg agagtttcca aagtcagctt 1080 agcccttcgg cggtcgcagg gactcgtttg cttgctgagt cccgctacaa cctggttgat 1140 cgcaataaca atatcgtact ggaataccag aaacaacaag tggttaagct gacgttgagc 1200 cctgcgacca tcagtggatt gcccggacaa gtttaccagg taaatgccca ggtccagggg 1260 gcctctgcgg ttcgcgaaat tgtctggtca gacgcagaat taatcgctgc aggaggcacc 1320 ttaacgccac tttccactac acaattcaat ttagtccttc ccccatacaa acgtaccgcc 1380 caggtatcgc gcgtaactga tgacttaact gctaattttt attcactgtc ggcgttagca 1440 gttgaccatc aaggcaaccg tagtaattcc ttcacattat ctgtaacggt gcagcagccg 1500 caactgacgc ttaccgcagc ggtcattggt gatggggccc cagctaatgg gaaaaccgca 1560 atcactgtcg agttcacagt tgcagatttt gaaggcaagc cgctggcggg tcaggaggtt 1620 gtgattacga ctaataacgg tgctcttcct aataagatta ctgaaaagac tgacgctaac 1680 ggcgttgccc gcattgccct tacgaacaca accgatgggg tcacggtagt taccgcagag 1740 gtcgaggggc aacgccaatc cgttgacacg cacttcgtta agggtactat cgcggccgat 1800 aaaagcacgc tggccgcggt 1820 <210> SEQ ID NO 1494 <211> LENGTH: 1977 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1494 atgattacgc atggctgtta tacccgtacg cgtcataaac acaagttgaa gaaaactctg 60 atcatgttat ccgctggact tggacttttt ttttacgtga atcagaactc tttcgctaat 120 ggggaaaatt attttaaact gggatcagac agcaaattac ttacgcatga ctcataccag 180 aatcgtctgt tttatacgct gaaaactggt gaaaccgttg cagatttaag taaaagtcag 240 gacattaacc tgtcaactat ttggtcactt aataaacact tatattcgag cgaatcggaa 300 atgatgaaag ctgcaccggg gcaacaaatc atcttgcccc tgaagaaatt gccctttgaa 360 tactccgctt tgcccttgct gggctcggct cctctggtag ccgccggagg cgttgccggt 420 cacactaata agctgacaaa aatgtcaccc gacgtgacga agagcaacat gacggatgat 480

aaggctttaa attacgcagc tcagcaagcg gcctcgttgg gaagtcagtt acagagtcgt 540 tcgttaaatg gtgattatgc taaggatacc gcattgggta ttgccggcaa ccaagcgtcg 600 agccaacttc aggcatggtt gcaacattac ggcactgctg aagtaaatct gcaatcaggt 660 aataattttg acggtagttc cctggatttc cttttacctt tttacgattc agaaaagatg 720 ttggctttcg gacaggtggg ggcgcgttac atcgattcac gttttaccgc taacttgggg 780 gccggtcaac gcttcttctt acctgccaat atgttgggct ataatgtatt tatcgaccag 840 gacttcagtg gtgacaatac acgtctggga attggtggag agtattggcg cgattacttt 900 aagtcatctg taaatggcta ttttcgcatg agcggttggc atgaaagtta caacaagaaa 960 gactacgatg agcgccccgc gaacgggttt gacatccgtt ttaatggtta tttgccatct 1020 tatcccgcct tgggagctaa attaatctac gagcaatact atggagataa cgtagctttg 1080 tttaatagcg acaagttaca gtctaatcca ggagcggcta cagtgggagt taattatacc 1140 ccaatcccac tggtcacaat gggaatcgat tatcgccacg ggactggtaa tgaaaacgat 1200 ttattatact ccatgcagtt tcgttatcag ttcgataaga gttggtcgca gcagattgag 1260 cctcaatatg ttaacgaatt acgtaccttg tccggcagtc gctacgatct ggtacaacgc 1320 aataacaata tcatccttga gtataagaaa caggacattc tgtctttgaa cattccacat 1380 gatattaatg gtaccgagca ctcaacacaa aaaattcagc tgattgtgaa atcaaagtat 1440 ggactggacc gtatcgtgtg ggatgatagc gctctgcgca gtcagggtgg acagatccag 1500 cactcgggta gccagtctgc ccaagactac caggctatcc tgccagcgta tgtccaaggg 1560 ggaagtaaca tctacaaagt tacagctcgc gcctatgacc gcaacggtaa ttctagtaat 1620 aatgtgcagt tgacaattac ggtgctgtcc aatgggcagg tcgtcgatca ggtaggtgtg 1680 acggatttta cagccgataa aacctctgcg aaggcagata acgcggatac catcacatac 1740 actgccactg taaaaaaaaa cggtgtcgcg caggcaaacg ttcctgttag cttcaacatc 1800 gtgtcgggta cagccaccct tggggccaac tcggcaaaga ctgacgcgaa tggcaaggct 1860 acagtcacgt tgaaatcctc gacaccagga caggtcgttg tgtctgccaa gacagcagag 1920 atgacctccg cccttaatgc atctgctgtt atcttcttcg atcaaacgaa ggcatct 1977 <210> SEQ ID NO 1495 <211> LENGTH: 705 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1495 tcggcattga cggaaggtgc aaaactgttt gagaaagaga tcccgtatat caccgaactg 60 gaaggcgacg tcgaaggtat gaaatttatc attaaaggcg agggtaccgg tgacgcgacc 120 acgggtacca ttaaagcgaa atacatctgc actacgggcg acctgccggt cccgtgggca 180 accctggtga gcaccctgag ctacggtgtt cagtgtttcg ccaagtaccc gagccacatc 240 aaggatttct ttaagagcgc catgccggaa ggttataccc aagagcgtac catcagcttc 300 gaaggcgacg gcgtgtacaa gacgcgtgct atggttacct acgaacgcgg ttctatctac 360 aatcgtgtca cgctgactgg tgagaacttt aagaaagacg gtcacattct gcgtaagaac 420 gttgcattcc aatgcccgcc aagcattctg tatattctgc ctgacaccgt taacaatggc 480 atccgcgttg agttcaacca ggcgtacgat attgaaggtg tgaccgaaaa actggttacc 540 aaatgcagcc aaatgaatcg tccgttggcg ggctccgcgg cagtgcatat cccgcgttat 600 catcacatta cctaccacac caaactgagc aaagaccgcg acgagcgccg tgatcacatg 660 tgtctggtag aggtcgtgaa agcggttgat ctggacacgt atcag 705 <210> SEQ ID NO 1496 <211> LENGTH: 705 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polynucleotide <400> SEQUENCE: 1496 acggcattga cggaaggtgc aaaactgttt gagaaagaga tcccgtatat caccgaactg 60 gaaggcgacg tcgaaggtat gaaatttatc attaaaggcg agggtaccgg tgacgcgacc 120 acgggtacca ttaaagcgaa atacatctgc actacgggcg acctgccggt cccgtgggca 180 accctggtga gcaccctgag ctacggtgtt cagtgtttcg ccaagtaccc gagccacatc 240 aaggatttct ttaagagcgc catgccggaa ggttataccc aagagcgtac catcagcttc 300 gaaggcgacg gcgtgtacaa gacgcgtgct atggttacct acgaacgcgg ttctatctac 360 aatcgtgtca cgctgactgg tgagaacttt aagaaagacg gtcacattct gcgtaagaac 420 gttgcattcc aatgcccgcc aagcattctg tatattctgc ctgacaccgt taacaatggc 480 atccgcgttg agttcaacca ggcgtacgat attgaaggtg tgaccgaaaa actggttacc 540 aaatgcagcc aaatgaatcg tccgttggcg ggctccgcgg cagtgcatat cccgcgttat 600 catcacatta cctaccacac caaactgagc aaagaccgcg acgagcgccg tgatcacatg 660 tgtctggtag aggtcgtgaa agcggttgat ctggacacgt atcag 705 <210> SEQ ID NO 1497 <211> LENGTH: 152 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1497 Cys Ser Ser Asn Lys Asn Ala Ser Asn Asp Gly Ser Glu Gly Met Leu 1 5 10 15 Gly Ala Gly Thr Gly Met Asp Ala Asn Gly Gly Asn Gly Asn Met Ser 20 25 30 Ser Glu Glu Gln Ala Arg Leu Gln Met Gln Gln Leu Gln Gln Asn Asn 35 40 45 Ile Val Tyr Phe Asp Leu Asp Lys Tyr Asp Ile Arg Ser Asp Phe Ala 50 55 60 Gln Met Leu Asp Ala His Ala Asn Phe Leu Arg Ser Asn Pro Ser Tyr 65 70 75 80 Lys Val Thr Val Glu Gly His Ala Asp Glu Arg Gly Thr Pro Glu Tyr 85 90 95 Asn Ile Ser Leu Gly Glu Arg Arg Ala Asn Ala Val Lys Met Tyr Leu 100 105 110 Gln Gly Lys Gly Val Ser Ala Asp Gln Ile Ser Ile Val Ser Tyr Gly 115 120 125 Lys Glu Lys Pro Ala Val Leu Gly His Asp Glu Ala Ala Tyr Ser Lys 130 135 140 Asn Arg Arg Ala Val Leu Val Tyr 145 150 <210> SEQ ID NO 1498 <211> LENGTH: 24 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <400> SEQUENCE: 1498 Met Thr Ser Ala Phe Asp Pro Asn Leu Val Gly Pro Thr Leu Pro Pro 1 5 10 15 Ile Pro Pro Phe Thr Leu Pro Thr 20 <210> SEQ ID NO 1499 <211> LENGTH: 147 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1499 Met Thr Ser Lys Ala Thr Lys Leu Val Leu Gly Ala Val Ile Leu Gly 1 5 10 15 Ser Thr Leu Leu Ala Gly Cys Ser Ser Asn Ala Lys Ile Asp Gln Gly 20 25 30 Ile Asn Pro Tyr Val Gly Phe Glu Met Gly Tyr Asp Trp Leu Gly Arg 35 40 45 Met Pro Tyr Lys Gly Ser Val Glu Asn Gly Ala Tyr Lys Ala Gln Gly 50 55 60 Val Gln Leu Thr Ala Lys Leu Gly Tyr Pro Ile Thr Asp Asp Leu Asp 65 70 75 80 Ile Tyr Thr Arg Leu Gly Gly Met Val Trp Arg Ala Asp Thr Lys Ser 85 90 95 Asn Val Tyr Gly Lys Asn His Asp Thr Gly Val Ser Pro Val Phe Ala 100 105 110 Gly Gly Val Glu Tyr Ala Ile Thr Pro Glu Ile Ala Thr Arg Leu Glu 115 120 125 Tyr Gln Trp Thr Asn Asn Ile Gly Asp Ala His Thr Ile Gly Thr Arg 130 135 140 Pro Asp Asn 145 <210> SEQ ID NO 1500 <211> LENGTH: 201 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1500 Met Thr Met Thr Arg Leu Lys Ile Ser Lys Thr Leu Leu Ala Val Met 1 5 10 15 Leu Thr Ser Ala Val Ala Thr Gly Ser Ala Tyr Ala Glu Asn Asn Ala 20 25 30 Gln Thr Thr Asn Glu Ser Ala Gly Gln Lys Val Asp Ser Ser Met Asn 35 40 45 Lys Val Gly Asn Phe Met Asp Asp Ser Ala Ile Thr Ala Lys Val Lys 50 55 60 Ala Ala Leu Val Asp His Asp Asn Ile Lys Ser Thr Asp Ile Ser Val 65 70 75 80

Lys Thr Asp Gln Lys Val Val Thr Leu Ser Gly Phe Val Glu Ser Gln 85 90 95 Ala Gln Ala Glu Glu Ala Val Lys Val Ala Lys Gly Val Glu Gly Val 100 105 110 Thr Ser Val Ser Asp Lys Leu His Val Arg Asp Ala Lys Glu Gly Ser 115 120 125 Val Lys Gly Tyr Ala Gly Asp Thr Ala Thr Thr Ser Glu Ile Lys Ala 130 135 140 Lys Leu Leu Ala Asp Asp Ile Val Pro Ser Arg His Val Lys Val Glu 145 150 155 160 Thr Thr Asp Gly Val Val Gln Leu Ser Gly Thr Val Asp Ser Gln Ala 165 170 175 Gln Ser Asp Arg Ala Glu Ser Ile Ala Lys Ala Val Asp Gly Val Lys 180 185 190 Ser Val Lys Asn Asp Leu Lys Thr Lys 195 200 <210> SEQ ID NO 1501 <211> LENGTH: 659 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1501 Met Ile Thr His Gly Cys Tyr Thr Arg Thr Arg His Lys His Lys Leu 1 5 10 15 Lys Lys Thr Leu Ile Met Leu Ser Ala Gly Leu Gly Leu Phe Phe Tyr 20 25 30 Val Asn Gln Asn Ser Phe Ala Asn Gly Glu Asn Tyr Phe Lys Leu Gly 35 40 45 Ser Asp Ser Lys Leu Leu Thr His Asp Ser Tyr Gln Asn Arg Leu Phe 50 55 60 Tyr Thr Leu Lys Thr Gly Glu Thr Val Ala Asp Leu Ser Lys Ser Gln 65 70 75 80 Asp Ile Asn Leu Ser Thr Ile Trp Ser Leu Asn Lys His Leu Tyr Ser 85 90 95 Ser Glu Ser Glu Met Met Lys Ala Ala Pro Gly Gln Gln Ile Ile Leu 100 105 110 Pro Leu Lys Lys Leu Pro Phe Glu Tyr Ser Ala Leu Pro Leu Leu Gly 115 120 125 Ser Ala Pro Leu Val Ala Ala Gly Gly Val Ala Gly His Thr Asn Lys 130 135 140 Leu Thr Lys Met Ser Pro Asp Val Thr Lys Ser Asn Met Thr Asp Asp 145 150 155 160 Lys Ala Leu Asn Tyr Ala Ala Gln Gln Ala Ala Ser Leu Gly Ser Gln 165 170 175 Leu Gln Ser Arg Ser Leu Asn Gly Asp Tyr Ala Lys Asp Thr Ala Leu 180 185 190 Gly Ile Ala Gly Asn Gln Ala Ser Ser Gln Leu Gln Ala Trp Leu Gln 195 200 205 His Tyr Gly Thr Ala Glu Val Asn Leu Gln Ser Gly Asn Asn Phe Asp 210 215 220 Gly Ser Ser Leu Asp Phe Leu Leu Pro Phe Tyr Asp Ser Glu Lys Met 225 230 235 240 Leu Ala Phe Gly Gln Val Gly Ala Arg Tyr Ile Asp Ser Arg Phe Thr 245 250 255 Ala Asn Leu Gly Ala Gly Gln Arg Phe Phe Leu Pro Ala Asn Met Leu 260 265 270 Gly Tyr Asn Val Phe Ile Asp Gln Asp Phe Ser Gly Asp Asn Thr Arg 275 280 285 Leu Gly Ile Gly Gly Glu Tyr Trp Arg Asp Tyr Phe Lys Ser Ser Val 290 295 300 Asn Gly Tyr Phe Arg Met Ser Gly Trp His Glu Ser Tyr Asn Lys Lys 305 310 315 320 Asp Tyr Asp Glu Arg Pro Ala Asn Gly Phe Asp Ile Arg Phe Asn Gly 325 330 335 Tyr Leu Pro Ser Tyr Pro Ala Leu Gly Ala Lys Leu Ile Tyr Glu Gln 340 345 350 Tyr Tyr Gly Asp Asn Val Ala Leu Phe Asn Ser Asp Lys Leu Gln Ser 355 360 365 Asn Pro Gly Ala Ala Thr Val Gly Val Asn Tyr Thr Pro Ile Pro Leu 370 375 380 Val Thr Met Gly Ile Asp Tyr Arg His Gly Thr Gly Asn Glu Asn Asp 385 390 395 400 Leu Leu Tyr Ser Met Gln Phe Arg Tyr Gln Phe Asp Lys Ser Trp Ser 405 410 415 Gln Gln Ile Glu Pro Gln Tyr Val Asn Glu Leu Arg Thr Leu Ser Gly 420 425 430 Ser Arg Tyr Asp Leu Val Gln Arg Asn Asn Asn Ile Ile Leu Glu Tyr 435 440 445 Lys Lys Gln Asp Ile Leu Ser Leu Asn Ile Pro His Asp Ile Asn Gly 450 455 460 Thr Glu His Ser Thr Gln Lys Ile Gln Leu Ile Val Lys Ser Lys Tyr 465 470 475 480 Gly Leu Asp Arg Ile Val Trp Asp Asp Ser Ala Leu Arg Ser Gln Gly 485 490 495 Gly Gln Ile Gln His Ser Gly Ser Gln Ser Ala Gln Asp Tyr Gln Ala 500 505 510 Ile Leu Pro Ala Tyr Val Gln Gly Gly Ser Asn Ile Tyr Lys Val Thr 515 520 525 Ala Arg Ala Tyr Asp Arg Asn Gly Asn Ser Ser Asn Asn Val Gln Leu 530 535 540 Thr Ile Thr Val Leu Ser Asn Gly Gln Val Val Asp Gln Val Gly Val 545 550 555 560 Thr Asp Phe Thr Ala Asp Lys Thr Ser Ala Lys Ala Asp Asn Ala Asp 565 570 575 Thr Ile Thr Tyr Thr Ala Thr Val Lys Lys Asn Gly Val Ala Gln Ala 580 585 590 Asn Val Pro Val Ser Phe Asn Ile Val Ser Gly Thr Ala Thr Leu Gly 595 600 605 Ala Asn Ser Ala Lys Thr Asp Ala Asn Gly Lys Ala Thr Val Thr Leu 610 615 620 Lys Ser Ser Thr Pro Gly Gln Val Val Val Ser Ala Lys Thr Ala Glu 625 630 635 640 Met Thr Ser Ala Leu Asn Ala Ser Ala Val Ile Phe Phe Asp Gln Thr 645 650 655 Lys Ala Ser <210> SEQ ID NO 1502 <211> LENGTH: 235 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1502 Thr Ala Leu Thr Glu Gly Ala Lys Leu Phe Glu Lys Glu Ile Pro Tyr 1 5 10 15 Ile Thr Glu Leu Glu Gly Asp Val Glu Gly Met Lys Phe Ile Ile Lys 20 25 30 Gly Glu Gly Thr Gly Asp Ala Thr Thr Gly Thr Ile Lys Ala Lys Tyr 35 40 45 Ile Cys Thr Thr Gly Asp Leu Pro Val Pro Trp Ala Thr Leu Val Ser 50 55 60 Thr Leu Ser Tyr Gly Val Gln Cys Phe Ala Lys Tyr Pro Ser His Ile 65 70 75 80 Lys Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Thr Gln Glu Arg 85 90 95 Thr Ile Ser Phe Glu Gly Asp Gly Val Tyr Lys Thr Arg Ala Met Val 100 105 110 Thr Tyr Glu Arg Gly Ser Ile Tyr Asn Arg Val Thr Leu Thr Gly Glu 115 120 125 Asn Phe Lys Lys Asp Gly His Ile Leu Arg Lys Asn Val Ala Phe Gln 130 135 140 Cys Pro Pro Ser Ile Leu Tyr Ile Leu Pro Asp Thr Val Asn Asn Gly 145 150 155 160 Ile Arg Val Glu Phe Asn Gln Ala Tyr Asp Ile Glu Gly Val Thr Glu 165 170 175 Lys Leu Val Thr Lys Cys Ser Gln Met Asn Arg Pro Leu Ala Gly Ser 180 185 190 Ala Ala Val His Ile Pro Arg Tyr His His Ile Thr Tyr His Thr Lys 195 200 205 Leu Ser Lys Asp Arg Asp Glu Arg Arg Asp His Met Cys Leu Val Glu 210 215 220 Val Val Lys Ala Val Asp Leu Asp Thr Tyr Gln 225 230 235 <210> SEQ ID NO 1503 <211> LENGTH: 470 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1503 Thr Ala Leu Thr Glu Gly Ala Lys Leu Phe Glu Lys Glu Ile Pro Tyr 1 5 10 15 Ile Thr Glu Leu Glu Gly Asp Val Glu Gly Met Lys Phe Ile Ile Lys 20 25 30 Gly Glu Gly Thr Gly Asp Ala Thr Thr Gly Thr Ile Lys Ala Lys Tyr 35 40 45 Ile Cys Thr Thr Gly Asp Leu Pro Val Pro Trp Ala Thr Leu Val Ser 50 55 60 Thr Leu Ser Tyr Gly Val Gln Cys Phe Ala Lys Tyr Pro Ser His Ile 65 70 75 80 Lys Asp Phe Phe Lys Ser Ala Met Pro Glu Gly Tyr Thr Gln Glu Arg 85 90 95 Thr Ile Ser Phe Glu Gly Asp Gly Val Tyr Lys Thr Arg Ala Met Val 100 105 110

Thr Tyr Glu Arg Gly Ser Ile Tyr Asn Arg Val Thr Leu Thr Gly Glu 115 120 125 Asn Phe Lys Lys Asp Gly His Ile Leu Arg Lys Asn Val Ala Phe Gln 130 135 140 Cys Pro Pro Ser Ile Leu Tyr Ile Leu Pro Asp Thr Val Asn Asn Gly 145 150 155 160 Ile Arg Val Glu Phe Asn Gln Ala Tyr Asp Ile Glu Gly Val Thr Glu 165 170 175 Lys Leu Val Thr Lys Cys Ser Gln Met Asn Arg Pro Leu Ala Gly Ser 180 185 190 Ala Ala Val His Ile Pro Arg Tyr His His Ile Thr Tyr His Thr Lys 195 200 205 Leu Ser Lys Asp Arg Asp Glu Arg Arg Asp His Met Cys Leu Val Glu 210 215 220 Val Val Lys Ala Val Asp Leu Asp Thr Tyr Gln Thr Ala Leu Thr Glu 225 230 235 240 Gly Ala Lys Leu Phe Glu Lys Glu Ile Pro Tyr Ile Thr Glu Leu Glu 245 250 255 Gly Asp Val Glu Gly Met Lys Phe Ile Ile Lys Gly Glu Gly Thr Gly 260 265 270 Asp Ala Thr Thr Gly Thr Ile Lys Ala Lys Tyr Ile Cys Thr Thr Gly 275 280 285 Asp Leu Pro Val Pro Trp Ala Thr Leu Val Ser Thr Leu Ser Tyr Gly 290 295 300 Val Gln Cys Phe Ala Lys Tyr Pro Ser His Ile Lys Asp Phe Phe Lys 305 310 315 320 Ser Ala Met Pro Glu Gly Tyr Thr Gln Glu Arg Thr Ile Ser Phe Glu 325 330 335 Gly Asp Gly Val Tyr Lys Thr Arg Ala Met Val Thr Tyr Glu Arg Gly 340 345 350 Ser Ile Tyr Asn Arg Val Thr Leu Thr Gly Glu Asn Phe Lys Lys Asp 355 360 365 Gly His Ile Leu Arg Lys Asn Val Ala Phe Gln Cys Pro Pro Ser Ile 370 375 380 Leu Tyr Ile Leu Pro Asp Thr Val Asn Asn Gly Ile Arg Val Glu Phe 385 390 395 400 Asn Gln Ala Tyr Asp Ile Glu Gly Val Thr Glu Lys Leu Val Thr Lys 405 410 415 Cys Ser Gln Met Asn Arg Pro Leu Ala Gly Ser Ala Ala Val His Ile 420 425 430 Pro Arg Tyr His His Ile Thr Tyr His Thr Lys Leu Ser Lys Asp Arg 435 440 445 Asp Glu Arg Arg Asp His Met Cys Leu Val Glu Val Val Lys Ala Val 450 455 460 Asp Leu Asp Thr Tyr Gln 465 470 <210> SEQ ID NO 1504 <211> LENGTH: 156 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1504 Ala Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly 1 5 10 15 Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser 20 25 30 Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe 35 40 45 Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser 50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val 65 70 75 80 Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr 85 90 95 Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr 100 105 110 Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Pro Ser 115 120 125 Thr Pro Pro Thr Pro Ser Pro Ser Thr Pro Pro Gly Leu Asn Asp Ile 130 135 140 Phe Glu Ala Gln Lys Ile Glu Trp His Gly Ser Ser 145 150 155 <210> SEQ ID NO 1505 <211> LENGTH: 149 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1505 Met Lys Tyr Leu Leu Pro Thr Ala Ala Ala Gly Leu Leu Leu Leu Ala 1 5 10 15 Ala Gln Pro Ala Met Ala Gln Val Gln Leu Val Glu Ser Gly Gly Gly 20 25 30 Leu Val Glu Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly 35 40 45 Ile Ile Phe Lys Ile Asn Asp Met Gly Trp Tyr Arg Gln Ala Pro Gly 50 55 60 Lys Arg Arg Glu Trp Val Ala Ala Ser Thr Gly Gly Asp Glu Ala Ile 65 70 75 80 Tyr Arg Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Ala Lys 85 90 95 Asn Ser Val Phe Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala 100 105 110 Val Tyr Tyr Cys Thr Ala Val Ile Ser Thr Asp Arg Asp Gly Thr Glu 115 120 125 Trp Arg Arg Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly 130 135 140 Gly Leu Pro Glu Thr 145 <210> SEQ ID NO 1506 <211> LENGTH: 70 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide <400> SEQUENCE: 1506 tcataaaaaa tttatttgct ttcaggaaaa tttttctgta taatagattc ataaatttga 60 gagaggagtt 70 <210> SEQ ID NO 1507 <211> LENGTH: 5 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic peptide <220> FEATURE: <223> OTHER INFORMATION: See specification as filed for detailed description of substitutions and preferred embodiments <400> SEQUENCE: 1507 Gly Gly Gly Gly Ser 1 5 <210> SEQ ID NO 1508 <211> LENGTH: 656 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1508 Met Ile Thr His Gly Cys Tyr Thr Arg Thr Arg His Lys His Lys Leu 1 5 10 15 Lys Lys Thr Leu Ile Met Leu Ser Ala Gly Leu Gly Leu Phe Phe Tyr 20 25 30 Val Asn Gln Asn Ser Phe Ala Asn Gly Glu Asn Tyr Phe Lys Leu Gly 35 40 45 Ser Asp Ser Lys Leu Leu Thr His Asp Ser Tyr Gln Asn Arg Leu Phe 50 55 60 Tyr Thr Leu Lys Thr Gly Glu Thr Val Ala Asp Leu Ser Lys Ser Gln 65 70 75 80 Asp Ile Asn Leu Ser Thr Ile Trp Ser Leu Asn Lys His Leu Tyr Ser 85 90 95 Ser Glu Ser Glu Met Met Lys Ala Ala Pro Gly Gln Gln Ile Ile Leu 100 105 110 Pro Leu Lys Lys Leu Pro Phe Glu Tyr Ser Ala Leu Pro Leu Leu Gly 115 120 125 Ser Ala Pro Leu Val Ala Ala Gly Gly Val Ala Gly His Thr Asn Lys 130 135 140 Leu Thr Lys Met Ser Pro Asp Val Thr Lys Ser Asn Met Thr Asp Asp 145 150 155 160 Lys Ala Leu Asn Tyr Ala Ala Gln Gln Ala Ala Ser Leu Gly Ser Gln 165 170 175 Leu Gln Ser Arg Ser Leu Asn Gly Asp Tyr Ala Lys Asp Thr Ala Leu 180 185 190 Gly Ile Ala Gly Asn Gln Ala Ser Ser Gln Leu Gln Ala Trp Leu Gln 195 200 205 His Tyr Gly Thr Ala Glu Val Asn Leu Gln Ser Gly Asn Asn Phe Asp 210 215 220 Gly Ser Ser Leu Asp Phe Leu Leu Pro Phe Tyr Asp Ser Glu Lys Met 225 230 235 240 Leu Ala Phe Gly Gln Val Gly Ala Arg Tyr Ile Asp Ser Arg Phe Thr 245 250 255 Ala Asn Leu Gly Ala Gly Gln Arg Phe Phe Leu Pro Ala Asn Met Leu 260 265 270

Gly Tyr Asn Val Phe Ile Asp Gln Asp Phe Ser Gly Asp Asn Thr Arg 275 280 285 Leu Gly Ile Gly Gly Glu Tyr Trp Arg Asp Tyr Phe Lys Ser Ser Val 290 295 300 Asn Gly Tyr Phe Arg Met Ser Gly Trp His Glu Ser Tyr Asn Lys Lys 305 310 315 320 Asp Tyr Asp Glu Arg Pro Ala Asn Gly Phe Asp Ile Arg Phe Asn Gly 325 330 335 Tyr Leu Pro Ser Tyr Pro Ala Leu Gly Ala Lys Leu Ile Tyr Glu Gln 340 345 350 Tyr Tyr Gly Asp Asn Val Ala Leu Phe Asn Ser Asp Lys Leu Gln Ser 355 360 365 Asn Pro Gly Ala Ala Thr Val Gly Val Asn Tyr Thr Pro Ile Pro Leu 370 375 380 Val Thr Met Gly Ile Asp Tyr Arg His Gly Thr Gly Asn Glu Asn Asp 385 390 395 400 Leu Leu Tyr Ser Met Gln Phe Arg Tyr Gln Phe Asp Lys Ser Trp Ser 405 410 415 Gln Gln Ile Glu Pro Gln Tyr Val Asn Glu Leu Arg Thr Leu Ser Gly 420 425 430 Ser Arg Tyr Asp Leu Val Gln Arg Asn Asn Asn Ile Ile Leu Glu Tyr 435 440 445 Lys Lys Gln Asp Ile Leu Ser Leu Asn Ile Pro His Asp Ile Asn Gly 450 455 460 Thr Glu His Ser Thr Gln Lys Ile Gln Leu Ile Val Lys Ser Lys Tyr 465 470 475 480 Gly Leu Asp Arg Ile Val Trp Asp Asp Ser Ala Leu Arg Ser Gln Gly 485 490 495 Gly Gln Ile Gln His Ser Gly Ser Gln Ser Ala Gln Asp Tyr Gln Ala 500 505 510 Ile Leu Pro Ala Tyr Val Gln Gly Gly Ser Asn Ile Tyr Lys Val Thr 515 520 525 Ala Arg Ala Tyr Asp Arg Asn Gly Asn Ser Ser Asn Asn Val Gln Leu 530 535 540 Thr Ile Thr Val Leu Ser Asn Gly Gln Val Val Asp Gln Val Gly Val 545 550 555 560 Thr Asp Phe Thr Ala Asp Lys Thr Ser Ala Lys Ala Asp Asn Ala Asp 565 570 575 Thr Ile Thr Tyr Thr Ala Thr Val Lys Lys Asn Gly Val Ala Gln Ala 580 585 590 Asn Val Pro Val Ser Phe Asn Ile Val Ser Gly Thr Ala Thr Leu Gly 595 600 605 Ala Asn Ser Ala Lys Thr Asp Ala Asn Gly Lys Ala Thr Val Thr Leu 610 615 620 Lys Ser Ser Thr Pro Gly Gln Val Val Val Ser Ala Lys Thr Ala Glu 625 630 635 640 Met Thr Ser Ala Leu Asn Ala Ser Ala Val Ile Phe Phe Asp Gly Ala 645 650 655 <210> SEQ ID NO 1509 <211> LENGTH: 131 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1509 Met Ala Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Ala 1 5 10 15 Gly Gly Ser Leu Leu Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser 20 25 30 Ser Tyr Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu 35 40 45 Phe Val Ala Ala Ile Asn Trp Ser Gly Gly Ser Thr Ser Tyr Ala Asp 50 55 60 Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Thr Lys Asn Thr 65 70 75 80 Val Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ala Phe 85 90 95 Tyr Cys Ala Ala Thr Tyr Asn Pro Tyr Ser Arg Asp His Tyr Phe Pro 100 105 110 Arg Met Thr Thr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr 115 120 125 Val Ser Ser 130 <210> SEQ ID NO 1510 <211> LENGTH: 139 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1510 Ala Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Ala Gly 1 5 10 15 Gly Ser Leu Leu Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser 20 25 30 Tyr Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe 35 40 45 Val Ala Ala Ile Asn Trp Ser Gly Gly Ser Thr Ser Tyr Ala Asp Ser 50 55 60 Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Thr Lys Asn Thr Val 65 70 75 80 Tyr Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ala Phe Tyr 85 90 95 Cys Ala Ala Thr Tyr Asn Pro Tyr Ser Arg Asp His Tyr Phe Pro Arg 100 105 110 Met Thr Thr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val 115 120 125 Ser Ser Glu Pro Lys Thr Pro Lys Pro Gln Pro 130 135 <210> SEQ ID NO 1511 <211> LENGTH: 124 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Description of Artificial Sequence: Synthetic polypeptide <400> SEQUENCE: 1511 Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly 1 5 10 15 Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr 20 25 30 Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val 35 40 45 Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val 50 55 60 Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp 65 70 75 80 Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys 85 90 95 Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp 100 105 110 Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser 115 120

Claims

1. A recombinant microorganism capable of displaying a displayed protein on its cell surface, wherein the microorganism expresses a display protein comprising an anchor domain, a linker, and the displayed protein.

2. The recombinant microorganism of claim 1, wherein the anchor domain is selected from the group containing, PelB-PAL, PAL, Intimin, YiaT, LppOmpA, BAN, OmsY, Invasin, IgA, PgsA, NGIgAsig-NGIgAb, and Ice nucleation protein.

3. The recombinant microorganism of claim 1, wherein the linker domain is selected from the group consisting of GGGGS (SEQ ID NO: 1477), (GGGGS)x2 (SEQ ID NO: 1478), (GGGGS)x3 (SEQ ID NO: 1479), EAAAK (SEQ ID NO: 1480), (EAAAK)x2 (SEQ ID NO: 1481), and (EAAAK)x3 (SEQ ID NO: 1482).

4. The recombinant microorganism of claim 1, wherein the displayed protein is a bacterial protein, a viral protein, a fungal protein, or a cancer protein.

5. The recombinant microorganism of claim 1, wherein the displayed protein is nanobody A4 or epidermal growth factor receptor (EGFR).

6. The recombinant microorganism of claim 1, wherein the recombinant bacterium comprises a gene encoding the display protein.

7. The recombinant microorganism of claim 6, wherein the gene encoding the display protein comprises a sequence encoding the anchor domain, a linker sequence, and a sequence encoding the displayed protein.

8. The recombinant microorganism of claim 1, wherein the displayed protein can induce an immune response in a subject.

9. A pharmaceutically acceptable composition comprising the recombinant microorganism of claim 1, and a pharmaceutically acceptable carrier.

10. A method of inducing and sustaining an immune response in a subject, the method comprising administering to the subject the pharmaceutically acceptable composition of claim 9, thereby inducing and sustaining the immune response in the subject.

11. A method of preventing and/or treating an infection in a subject, the method comprising administering to the subject the pharmaceutically acceptable composition of claim 9, thereby preventing and/or treating the infection in the subject.

12. A method of inducing and sustaining an immune response in a subject, the method comprising administering a first recombinant microorganism to the subject, wherein the first recombinant microorganism is capable of displaying a displayed protein on its cell surface; and administering a second recombinant microorganism to the subject, wherein the second recombinant microorganism is capable of producing an immune modulator, thereby inducing and sustaining the immune response in the subject.

13. A method of preventing and/or treating a microbial infection in a subject, the method comprising administering a first recombinant microorganism to the subject, wherein the first recombinant microorganism is capable of displaying a displayed protein on its cell surface; and administering a second recombinant microorganism to the subject, wherein the second recombinant microorganism is capable of producing an immune modulator, thereby preventing and/or treating the microbial infection in the subject.

14. A method of inducing and sustaining an immune response in a subject, the method comprising administering a recombinant microorganism to the subject, wherein the recombinant microorganism is capable of producing a protein and an immune modulator, thereby inducing and sustaining the immune response in the subject.